Inverting thrombectomy apparatuses having enhanced tracking

ABSTRACT

Mechanical thrombectomy apparatuses, and particularly knitted rolling tube mechanical thrombectomy apparatuses configured to have improved tracking for delivery through tortious vessels are described herein. Also described herein are methods of removing clots using a mechanical thrombectomy apparatuses in which the clot is larger than the tractor portion of the mechanical thrombectomy apparatus.

RELATED APPLICATION DATA

This patent application claims priority to U.S. provisional patentapplication No. 62/583,803, filed on Nov. 9, 2017 and titled “INVERTINGTHROMBECTOMY APPARATUSES HAVING ENHANCED TRACKING”; and U.S. provisionalpatent application No. 62/664,822, filed on Apr. 30, 2018, and titled“INVERTING THROMBECTOMY APPARATUSES HAVING ENHANCED TRACKING”.

This application is related to each of: U.S. application Ser. No.15/291,015, filed Oct. 11, 2016, entitled “Mechanical ThrombectomyApparatuses and Methods”; U.S. application Ser. No. 15/496,570, filedApr. 25, 2017, entitled “Anti-Jamming and Macerating ThrombectomyApparatuses and Methods”; U.S. application Ser. No. 15/496,668, filedApr. 25, 2017, entitled “Pre-loaded inverting tractor ThrombectomyApparatuses and Methods”; U.S. application Ser. No. 15/496,786, filedApr. 25, 2017, entitled “Methods for Advancing Inverting MechanicalThrombectomy Apparatuses in The Vasculature”; U.S. application Ser. No.15/497,092, filed Apr. 25, 2017, entitled “Clot-Engulfing MechanicalThrombectomy Apparatuses and Methods of use”; and U.S. application Ser.No. 15/611,546, filed Jun. 1, 2017, entitled “Inverting ThrombectomyApparatuses And Methods.” The foregoing patent applications are eachherein incorporated by reference in their entirety.

FIELD

The apparatuses and methods described herein relate to mechanicalremoval of objects from within a body. In particular, described hereinare mechanical thrombectomy apparatuses and methods.

BACKGROUND

Many vascular problems stem from insufficient blood flow through bloodvessels. One causes of insufficient or irregular blood flow is ablockage within a blood vessel referred to as a blood clot, or thrombus.Thrombi can occur for many reasons, including after a trauma such assurgery, or due to other causes. For example, a large percentage of themore than 1.2 million heart attacks in the United States are caused byblood clots (thrombi) which form within a coronary artery. It is oftendesirable to remove tissue from the body in a minimally invasive manneras possible, so as not to damage other tissues. For example, removal oftissue, such as blood clots, from within a patient's vasculature mayimprove patient quality of life.

Mechanical thrombectomy devices may be particularly advantageous. Thereis a definite need for thrombectomy devices, and particularly amechanical thrombectomy devices that can be easily and accuratelydelivered through the, often tortious, anatomy in the peripheral andcentral vasculature, then reliably deployed to remove clot material.Described herein are apparatuses (devices, systems and kit) and methodsof using them that may address the needs and problems discussed above.

SUMMARY

Described herein are inverting tractor mechanical thrombectomyapparatuses (devices, systems, etc.) and methods of using and makingthem.

In particular, described herein are inverting tractor mechanicalthrombectomy apparatuses that are configured to have improved trackingwithin even the most tortious vessels of the anatomy. These invertingtractor mechanical thrombectomy apparatuses may be referred to herein asmechanical thrombectomy apparatuses. The method and apparatusesdescribed herein may include the use of a deliver catheter (e.g.,“intermediate catheter”) that is pre-loaded with the mechanicalthrombectomy apparatus in a specific arrangement that provides enhancestracking, and methods of using them to reach, and remove, clot.

Also described herein are adaptations to mechanical thrombectomyapparatuses that allow them to remove particularly large clots withoutbreaking or disrupting the clot, even if the rolling tractor portion ofthe mechanical thrombectomy apparatus is not able to pull additionalclot into the apparatus.

Typically, the mechanical thrombectomy apparatuses described herein areinverting thrombectomy apparatuses (also referred to herein as invertingtractor thrombectomy apparatuses and inverting tube thrombectomyapparatuses) that include a flexible tube (e.g., tractor tube, tractorregion, tractor portion, etc.) and an elongate inversion supportcatheter. The tractor tube generally comprises a flexible tube ofmaterial that inverts over itself as it rolls over a distal end openingof an elongate inversion support. The flexible tube may be formed of aknitted material, and may be configured (e.g., sized, oriented, etc.) toroll smoothly over the distal end opening of the elongate inversionsupport catheter. The flexible tube may be configured so that it isdoubly biased, in order to prevent jamming and to grab and compressrelatively large clots as it rolls and inverts into the elongateinversion support catheter at the distal end opening of the elongateinversion support catheter; the flexible tube may be biased so that ithas an expanded (e.g., relaxed) un-inverted configuration having anouter diameter that is approximately the same or slightly larger thanthe inner diameter of the elongate inversion support catheter, which maybe referred to as a second configuration of the flexible tube. Theflexible tube may also be further biased so that it has an expanded(e.g., relaxed) inverted configuration (which may be referred to as afirst configuration) having an inner and outer diameter that is largerthan the outer diameter of the elongate inversion support catheter. Theinner diameter in this first configuration may be greater than 1.2×(e.g., between 1.2× and 10×, between 1.2× and 8×, between 1.2× and 6×,between 1.2× and 5×, between 1.2× and 3×, etc.) the outer diameter ofthe inversion support catheter. Thus, when the flexible tube is placedin and over the distal end of the inversion support catheter, a first(inner) portion of the tractor tube is within the distal end of theelongate inversion support catheter in the un-inverted configuration andit is biased to expand towards (and in some configuration against) theinner diameter of the inversion support catheter; the region of theflexible tube that is inverted over the distal end opening of theinversion support catheter and extends proximally down the outside ofthe inversion support catheter is in an inverted configuration in whichthe inner diameter of the flexible tube is biased to be larger than theouter diameter of the inversion support catheter. This double-biasedconfiguration may be a result of the weave pattern (e.g., knitting),and/or a shape setting of the material forming the tractor tube, whichmay be a shape memory material. As a result, the inverting portion ofthe flexible tube, where it rolls and inverts over itself at the distalend of the inversion support catheter may be prevented from collapsingon itself as the tractor tube is rolled and pulled into the inversionsupport catheter. In some variations this configuration may also resultin a somewhat flattened (e.g., and in some cases “trumpet shaped”)distal end face that is rolling over the distal end opening of theelongate inversion support catheter. The trumpet-shaped distal end mayhave a teardrop-shaped cross-section. In some variations, the distal endface of the flexible tube may be T-shaped.

Also described herein are variations in which the first configuration ofthe flexible tube on the outside of the inversion support catheter(which may be referred to herein as an elongate inversion supportcatheter) maybe flush or nearly flush with the outer diameter of theinversion support catheter, e.g., within 50%, 40%, 30%, 20%, etc. of theouter diameter of the inversion support catheter.

The flexible tube may be coupled to a puller that is within the lumen ofthe inversion support. The puller may be a wire, filament, rod or morepreferably a catheter or tube (and may be referred to herein as a pullmicro catheter or “PMC” for convenience). A guidewire may be passedthrough the flexible tube, and therefore through the inversion supportand the tractor tube. As will be described herein, this may be used forpositioning.

The inversion support catheter may be configured as a catheter having adistal end opening into which the tractor inverts. The flexible tube mayinvert and rolls back into itself and may be drawn into the inversionsupport in a conveyor-like motion; the outward-facing region rollsaround to become an inward-facing region, e.g., within the lumen of theinversion support catheter. The rolling motion may thus draw a clot orother object within a vessel into the inversion support. The inversionsupport catheter may be shaped or configured to have a sufficient columnstrength to withstand the compressive pulling force of the flexible tubeas it is drawn (and rolled, inverting) into the distal end of theinversion support catheter. The inversion support catheter may beslotted (e.g., may include a plurality of slots or openings) to provideincreased flexibility as well as column strength. However, as will bedescribed herein, many inversion support catheters may become lessflexible (e.g., more rigid) when a compressive force is applied to theflexible tube, either as a result of pulling the flexible tubeproximally, either from within the inversion support catheter, or fromthe outside of the inversion support catheter as the flexible tubebrushes against the vessel and/or a delivery catheter when being drivendistally towards a clot.

Thus, described herein are mechanical inverting thrombectomy apparatusesthat are adapted to enhance tracking as the apparatus is positionedwithin the vessel by pushing it distally away from an insertion pointinto the body to the site of the thrombus. These apparatuses and methodsmay include pre-loading the apparatus within an intermediate catheter ina particular configuration allowing it to track more easily, as well asvariations in which the flexible tube is held within the inversionsupport catheter and deployed near the clot. Finally, described hereinare apparatus in which the flexible tube (e.g., mesh, weave, knit) tolimit or prevent the application of a compressive force on the inversionsupport catheter that may otherwise reduce flexibility andmaneuverability of the inversion support catheter.

Also described herein are methods and apparatuses for removing extensiveclots, even when the flexible tube portion of the apparatus has beencompletely inverted, without breaking the clot and risking release ofthe clot back into the bloodstream where it could cause further harm.

For example, described herein are methods and apparatuses that use oneor more vacuum sources that may be applied either or both when initiallycontacting a clot and/or when removing the clot after being completelyor partially engulfed by the flexible tube (tractor) portion of theapparatuses described herein. These methods and apparatuses may be usedwith any of the apparatuses and methods described herein, for example,in above-incorporated U.S. application Ser. Nos. 15/291,015 and15/496,570.

A method of removing a clot from a vessel may include: advancing aninverting tube apparatus through a vessel until a distal end of theinverting tube apparatus is proximate to a clot, wherein the invertingtube apparatus comprises an intermediate catheter, an inversion supportcatheter within a lumen of the intermediate catheter, a puller catheterwithin a lumen of the elongate support catheter, and a flexible tubehaving a first end coupled at a distal end region of the pullercatheter, wherein flexible tube inverts over a distal end of theinversion support catheter and extends proximally between theintermediate catheter and the inversion support catheter; advancing thepuller catheter distally so that a distal face of puller catheterextends distally from the inverting tube apparatus; applying a vacuumthrough the puller catheter to engage the clot with the distal face ofthe puller catheter; and pulling the puller catheter proximally to rollthe flexible tube over a distal end of the inversion support catheter sothat the flexible tube inverts over the distal end of the inversionsupport catheter captures the clot and pulls the clot proximally intothe inversion support catheter.

The inverting tube apparatus (e.g., a mechanical thrombectomy apparatus)may be inserted through a vessel such as a blood vessel, artery, etc.,until a distal end, or a distal-most end, of the inverting tubeapparatus is proximate to a clot. The clot may be immediately adjacentto the end of the apparatus, or it may be within a few cm (e.g., within1 cm, within 2 cm, within 3 cm, within 4 cm, etc.). This may be detectedby visualization, such as fluoroscopy. Thus, the apparatuses describedherein may include one or more markers for visualization. Contrast maybe used to visualize the clot and/or may be released from the apparatus.The apparatus may be deployed in a pre-loaded/pre-assembledconfiguration, as will be described in more detail below.

In any of these methods described herein, the flexible tube may beknitted and/or the apparatus may be configured with the opening into thevacuum lumen (e.g., through the puller catheter) at the distal-most endof the device, so that the flexible tube extends behind (proximal) thedistal-facing end of the puller catheter. For example, the method ofremoving a clot from a vessel may include: advancing an inverting tubeapparatus through a vessel until a distal end of the inverting tubeapparatus is proximate to a clot, wherein the inverting tube apparatuscomprises an intermediate catheter, an inversion support catheter withina lumen of the intermediate catheter, a puller catheter within a lumenof the elongate support catheter, and a knitted tube having a first endcoupled at a distal end region of the puller catheter, wherein knittedtube inverts over a distal end of the inversion support catheter andextends proximally between the intermediate catheter and the inversionsupport catheter, further wherein the knitted tube comprises a filamentthat is knitted to form a plurality of interlocking loop stitches;advancing the puller catheter distally so that a distal face of pullercatheter extends distally from the inverting tube apparatus further thanthe knitted tube; applying a vacuum through the puller catheter toengage the clot with the distal face of the puller catheter; and pullingthe puller catheter proximally to roll the knitted tube over a distalend of the inversion support catheter so that the knitted tube invertsover the distal end of the inversion support catheter, captures theclot, and pulls the clot proximally into the inversion support catheter.

Thus, in any of these variations, advancing the puller catheter distallymay include advancing the puller catheter so that a distal face ofpuller catheter extends distally from the inverting tube apparatusfurther than the flexible tube. Advancing the inverting tube apparatusmay comprise advancing over a guidewire passing through the pullercatheter of the inverting tube apparatus. Advancing the puller catheterdistally may further comprise advancing the elongate support catheterdistally between the flexible tube and the puller catheter. Advancingthe inverting tube apparatus comprises advancing the puller and flexibletube distally in the vessel, wherein the flexible tube extendsproximally from the distal end region and further wherein the flexibletube comprises a knitted tube comprising a filament that is knitted toform a plurality of interlocking loop stitches.

Any of these methods may also include withdrawing the intermediatecatheter proximally before or while advancing the puller catheterdistally.

In general, applying the vacuum may include applying the vacuum throughthe puller catheter and around a guidewire within the puller catheter.When a guidewire is used, it may be threaded through the pullercatheter; the vacuum may be applied with the guidewire present or it maybe removed first. For example, the method may include removing aguidewire from out of the puller catheter prior to applying the vacuum.

The vacuum (suction) applied may also be used to help guide the therapyand operation of the apparatus. For example, any of these methods mayinclude observing flow from the puller catheter when applying the vacuumto determine when the clot is engaged with the distal face of the pullercatheter. The vacuum may be applied concurrently with advancing thepuller catheter distally; once the clot is contacted (which may bedetected, e.g., by monitoring the vacuum resistance and/or the flowthrough the puller catheter), the vacuum may be sustained, reduced, orturned off.

In some variations, vacuum may be applied through the intermediatecatheter while withdrawing the puller catheter and puller proximallyinto the intermediate catheter.

Also described herein are methods and apparatus for removinglonger/larger clots from a vessel. In particular, described herein aremethods and apparatuses for removing clots that are longer than theflexible tube portion of the apparatus.

For example, described herein are methods of removing a large clot froma vessel, the method comprising: advancing an inverting tube apparatusthrough a vessel until a distal end of the inverting tube apparatus isproximate to a clot, wherein the inverting tube apparatus comprises anintermediate catheter, an inversion support catheter within a lumen ofthe intermediate catheter, a puller within a lumen of the inversionsupport catheter, and a flexible tube having a first end coupled at adistal end region of the puller and a second end that is free to moveover an outer surface of the inversion support catheter, wherein theflexible tube extends proximally between the intermediate catheter andthe inversion support catheter; pulling the puller proximally to rollthe flexible tube over the distal end of the inversion support catheterso that the flexible tube inverts over a distal end of the inversionsupport catheter, captures the clot, and pulls the clot proximally intothe inversion support catheter, wherein the second end reaches thedistal end of the inversion support catheter while a portion of the clotextends distally from the inversion support catheter; and withdrawing,after the second end reaches the distal end of the inversion supportcatheter, the inversion support catheter and puller with the clotattached proximally into the intermediate catheter until the entire clotis within the intermediate catheter.

For example, a method of removing a clot from a vessel may include:advancing an inverting tube apparatus through a vessel until a distalend of the inverting tube apparatus is proximate to a clot, wherein theinverting tube apparatus comprises an intermediate catheter, aninversion support catheter within a lumen of the intermediate catheter,a puller within a lumen of the elongate support catheter, and a flexibletube having a first end coupled at a distal end region of the puller anda second end comprising a cuff that is less flexible that a region ofthe flexible tube adjacent to the cuff, wherein the flexible tubeextends proximally between the intermediate catheter and the inversionsupport catheter; pulling the puller proximally to roll the flexibletube over the distal end of the inversion support catheter so that theflexible tube inverts over a distal end of the inversion supportcatheter, captures the clot, and pulls the clot proximally into theinversion support catheter; stopping pulling the puller from movingproximally when or before the cuff reaches the distal end of theinversion support catheter; moving the intermediate catheter distallypast the cuff to invert the cuff over the distal end of the inversionsupport catheter; and withdrawing the inversion support catheter andpuller with the clot attached proximally into the intermediate catheter.

A large clot may be a clot that is typically longer than the capacity ofthe apparatus to hold within the flexible tube. This is described ingreater detail herein, but may be, e.g., a 12:1 ratio (where, for every12 cm of, e.g., woven, flexible tube, 1 cm of length of clot may becontained within the woven flexible tube). In general, large clots mayhave a large diameter and/or a long length. Longer clots may includeclots having a length that is about 0.5 m or longer (e.g., about 1 cm orlonger, about 2 cm or longer, about 3 cm or longer, about 4 cm orlonger, about 5 cm or longer, etc.).

In any of the methods described herein, the second end may reach thedistal end of the inversion support catheter while a portion of the clotextends distally from the inversion support catheter so that at least aportion of the clot extends out of the flexible tube. The second end ofthe flexible tube may be prevented (stopped) from inverting over the endof the inversion support catheter, or it may be inverted and flipped(e.g., by advancing the intermediate catheter) in a non-traumatic waythat prevents or limits the risk of breaking/tearing/disrupting theclot.

In any of these variations, suction may be applied through the invertingtube apparatus (e.g., through the intermediate catheter and/or theinversion support catheter) when withdrawing the inversion supportcatheter and puller with the clot attached proximally into theintermediate catheter.

The second end of the flexible tube may comprise a cuff that is lessflexible that a region of the tube adjacent to the cuff. As will bedescribed in more detail below, the cuff may be formed as a materialattached to or applied onto/over the end of the flexible tube. Forexample, the second end of the flexible tube may comprise a cuff formedof a polymeric material applied onto/over the knitted tube. The cuff maybe slit or cut (e.g., all or partially along its length) to provide someflexibility when pulling over or around the end of the tube. Forexample, the cuff may include longitudinal slits along its length. Thecuff may have a durometer that is greater than the durometer of theflexible tube (e.g., knitted tube). The cuff, in some variations, isthicker than the flexible tube. In any of the variations describedherein, the cuff may be radiopaque (e.g., by including a radiopaquematerial, such as platinum) on or within the cuff.

As mentioned, the apparatus may be configured so that the end (e.g., thesecond end) of the flexible tube may be prevented from inverting androlling over the distal end of the inversion support catheter by simplypulling proximally on the puller. Thus, in any of these variations, theintermediate catheter may be configured to push the cuff over the distalend of the inversion support catheter when the intermediate catheter isadvanced distally past the cuff

As mentioned, any of these methods may include limiting the puller tostop the puller from moving proximally when or before the cuff reachesthe distal end of the inversion support catheter. The limiting may beachieved by the cuff or other member (e.g., protrusion) engaging a stop(e.g., on the inversion support catheter) or the like. Any of thesemethods may include moving the intermediate catheter distally past thecuff to invert the cuff over the distal end of the inversion supportcatheter.

Specifically described herein are methods and apparatuses using flexibleknitted tubes (tractors) as part of any of the mechanical thrombectomyapparatuses described herein. For example, the knitted flexible tubesmay be configured to have stitch lengths that assist in capturing ofclot within the vessel, even where the vessel has a larger innerdiameter than the outer diameter of the flexible tube in an expandedconfiguration outside of the inversion support catheter. In particular,apparatuses in which the stich length is within a range of lengths thatmay be set by the dimension of the vessel (e.g., blood vessel, artery,peripheral vessel, etc.) and/or the outer diameter of the inversionsupport catheter. For example, a stitch length may be between about 0.5mm and 10 mm and/or may be selected based on the dimension of the vesselinto which the apparatus is to be operated to remove a clot.

For example, described herein are method of removing a clot from avessel having an inner diameter (ID), the method comprising: advancingan inverting tube apparatus through the vessel until a distal end of theinverting tube apparatus is proximate to a clot, wherein the invertingtube apparatus comprises an intermediate catheter, an inversion supportcatheter within a lumen of the intermediate catheter, a puller within alumen of the support catheter, and a knitted tube having a first endcoupled at a distal end region of the puller and a second end, whereinthe knitted tube extends between the intermediate catheter and theinversion support catheter; further wherein the knitted tube comprises afilament knitted to form a plurality of interlocking loop stitches,wherein each loop stitch has a stitch length that is between thedifference of 25% of the ID and one half the outer diameter (OD) of theinversion support catheter and 65% of the ID and one half of the OD ofthe inversion support catheter; pulling the puller proximally to rollthe knitted tube over the distal end of the inversion support catheterso that the knitted tube inverts over a distal end of the inversionsupport catheter driving the loop stitches outward, captures the clot,and pulls the clot proximally into the inversion support catheter.

Any of these methods may be used in particular with apparatuses in whichthe flexible tube is configured to remain relative snug on the inversionsupport catheter (e.g., within 50% (e.g., 40%, 30%, 25%, 20%, 15%, 10%,etc.) of the outer diameter of the inversion support catheter in theexpanded (unconstrained) first configuration. In general, theseapparatuses may expand at or near the distal-facing ends of the flexibletube, where the tube is inverting over itself, but may not be expandedat more proximal regions. This may form the T-shaped, Y-shaped, and/ortrumpet-shaped distal end faces of the flexible tubes described herein.For example, in some variations, the knitted tube extends over theinversion support catheter with an inner diameter that is within 20% ofthe OD the inversion support catheter.

The second end of the knitted tube may comprise a cuff that is lessflexible that a region of the knitted tube adjacent to the cuff, asdescribed above and further herein. Alternatively, or additionally, theknitted tube may be shape-set to have a narrower region at the secondend region (near the second end) of the flexible tube.

As mentioned above, in general, each loop stitch may have a stitchlength that is between the difference of 25% of the ID and one half theouter diameter (OD) of the inversion support catheter and 65% of the IDand one half of the OD of the inversion support catheter. For example,each loop stitch may have a stitch length that is between the differenceof 30% of the ID and one half the OD of the inversion support catheterand 60% of the ID and one half of the OD of the inversion supportcatheter (e.g., between the difference of 35% of the ID and one half theOD of the inversion support catheter and 50% of the ID and one half ofthe OD of the inversion support catheter, between the difference of 40%of the ID and one half the OD of the inversion support catheter and 45%of the ID and one half of the OD of the inversion support catheter,between the difference of 25% of the ID and one half the OD of theinversion support catheter and 45% of the ID and one half of the OD ofthe inversion support catheter, etc.). The stitch length may refer tothe longitudinal (in the proximal-to-distal axis, which may curve orbend) of the knitted tube. The knitted tube may be formed of one or morefilaments (or filament bundles) that are knitted into the tube to forminterlocking links (loop stitches). The filament material may berelatively stiff, such as a wire, e.g., Nitinol wire, that when knittedhas a material flexibility. The knit may be coated with a material(e.g., a lubricious material, etc.). Examples of knits are illustratedin, e.g., U.S. application Ser. No. 15/496,570, filed on Apr. 25, 2017(“Anti-Jamming and Macerating Thrombectomy Apparatuses and methods”),previously incorporated by reference in its entirety.

For example, an inverting tube apparatus for removing a clot from avessel may include: an intermediate catheter; an inversion supportcatheter within a lumen of the intermediate catheter; a puller within alumen of the elongate support catheter; and a knitted tube extendingover the inversion support catheter, the knitted tube having a first endcoupled at a distal end region of the puller and a second end that isfree, wherein the knitted tube is configure to be pulled proximally intothe inversion support catheter by pulling the puller proximally so thatthe knitted tube rolls and inverts over a distal end of the inversionsupport catheter; further wherein the knitted tube comprises a filamentknitted to form a plurality of interlocking loop stitches, wherein eachloop stitch has a stitch length that is between 0.5 mm and 10 mm.

As mentioned, the knitted tube may extend over the inversion supportcatheter with an inner diameter that is within 20% (e.g., within about10%, 15%, 20%, 25%, 30%, 40%, etc.) of the outer diameter of theinversion support catheter (e.g., relatively snugly to or against theinversion support catheter). The second end of the knitted tube maycomprise a cuff that is less flexible that a region of the knitted tubeadjacent to the cuff.

Any of the methods and apparatuses described herein may include anexpanded flexible tube portion that expands outward less than thediameter of the vessel over much (e.g., greater than about 50%, about60%, about 70%, about 75%, about 80%, about 90%, etc.) of its lengthwhile having an expanded second end region that has a much smallerdiameter near this second end region (e.g., having a diameter that iswithin about 10%, 15%, 20%, 25%, 30%, 40%, etc. of the inversion supportcatheter. This configuration may allow even larger-diameter clots (e.g.,from the peripheral vasculature) to be engulfed and safely removed withapparatuses having a much narrower diameter than the vessels in whichthe clots are located.

For example, described herein are inverting tube apparatus for removinga clot from a vessel, the apparatus comprising: an inversion supportcatheter; a puller within a lumen of the inversion support catheter; anda knitted tube extending over the inversion support catheter in a firstconfiguration, the knitted tube having a first end coupled to a distalend region of the puller, and a second end that is free to move relativeto the inserting support catheter, wherein the knitted tube is configureto be pulled proximally into the inversion support catheter by pullingthe puller proximally so that the knitted tube rolls and inverts over adistal end of the inversion support catheter into a second configurationwithin the inversion support catheter; further wherein the knitted tubein the first configuration has an expanded outer diameter that isbetween 0.5 mm and 12 mm for a first region of the knitted tube that isadjacent to the first end, and the knitted tube in the secondconfiguration has an inner diameter that is greater than 30% of an innerdiameter of the inversion support catheter, and wherein a second regionof the knitted tube adjacent to the second end has an expanded outerdiameter that is less than the expanded outer diameter of the region ofthe knitted tube adjacent to the first end and within 20% of an outerdiameter of the inversion support catheter.

As mentioned, the knitted tube in the first configuration may have anexpanded outer diameter (unconstrained) that is between 0.5 mm and 12mm; in some variations this expanded outer diameter is between 0.5 mmand 15 mm, e.g., between about 0.5 mm and about 14 mm, between about 0.5mm and about 13 mm, between about 0.5 mm and about 11 mm, between about0.5 mm and about 10 mm, between about 0.5 mm and about 9 mm, betweenabout 0.5 mm and about 8 mm, between about 3 mm and about 15 mm, betweenabout 4 mm and about 15 mm, between about 5 mm and about 15 mm, betweenabout 3 mm and about 12 mm, between about 4 mm and about 12 mm, betweenabout 5 mm and about 12 mm, between about 3 mm and about 10 mm, betweenabout 4 mm and about 10 mm, between about 5 mm and about 10 mm, etc.

Any of the apparatuses described herein may include a cuff at the secondend, wherein the cuff has a stiffness that is greater than a region ofthe knitted tube adjacent to the cuff. Alternatively, or additionally,any of these apparatuses may include a stop configured to limit thetravel of the knitted tube so that the second end does not roll andinvert over the distal end of the inversion support catheter.

The knitted tube may be shape set so that the first configuration hasthe outer diameter between, e.g., 0.5 mm and 10 mm for the region of thekitted tube adjacent to the first end, and the knitted tube in thesecond configuration has an inner diameter that is greater than, e.g.,about 30% (e.g., about 40%, about 50%, about 60%, etc.) of the innerdiameter of the inversion support catheter.

The first region of the kitted tube (having the larger expandeddiameter) may be any appropriate length (e.g., at least about 0.5 cm,about 1 cm, about 2 cm, about 3 cm, about 4 cm, about 5 cm, about 6 cm,about 7 cm, about 8 cm, about 9 cm, about 10 cm, etc.). Similarly, thesecond region (having the narrower expanded diameter) may be anyappropriate length (e.g., at least about 0.5 cm, about 1 cm, about 2 cm,about 3 cm, about 4 cm, about 5 cm, etc.).

The knitted tube may comprise a filament knitted to form a plurality ofinterlocking loop stitches, wherein each loop stitch has a stitch lengththat is between a predetermined range (e.g., between about 0.5 mm and 8mm, about 0.5 to 10 mm, about 0.5 mm to 12 mm, about 0.5 to 14 mm,etc.). This may permit, for example, at a region of the knitted tubethat is inverting from the first configuration to the secondconfiguration, a sub-set of the plurality of loop stitches forming theknitted tube may extend proud from the long axis of the knitted tube bybetween 0.5 mm and 10 mm (e.g., between about 0.3 mm and about 8 mm,between about 0.5 mm and about 8 mm, between about 0.5 mm and about 7mm, between about 0.5 mm and about 6 mm, greater than about 1 mm,greater than about 2 mm, greater than about 3 mm, greater than about 4mm, greater than about 5 mm, etc.) as the knitted tube inverts.

Any of these apparatuses may include an intermediate catheter having alumen as described herein. The inversion support catheter may be withinthe lumen of the intermediate support catheter and may be extendeddistally from the intermediate catheter to deploy the knitted tube sothat the flexible tube may expand into the first configuration.

As mentioned, described herein are methods for removing a clot from avessel a larger diameter (and therefore a larger clot diameter) thaneven the expanded flexible tube of the apparatus. For example, describedherein are methods of removing a clot from a vessel having an innerdiameter (ID) comprising: advancing an inverting tube apparatus throughthe vessel until a distal end of the inverting tube apparatus isproximate to a clot, wherein the inverting tube apparatus comprises aninversion support catheter, a puller within a lumen of the supportcatheter, and a knitted tube having a first end coupled to a distal endregion of the puller, and a second end that is free to move relative tothe inserting support catheter, wherein the knitted tube comprises afilament knitted to form a plurality of interlocking loop stitches,wherein each loop stitch has a stitch length; expanding the knitted tubeto a first configuration along an outer surface of the inverting tubecatheter to an outer diameter that between 10% and 80% of an innerdiameter of the vessel for a first region of the knitted tube that isadjacent to the first end, wherein the knitted tube has a secondconfiguration within the inverting tube catheter having an innerdiameter that is greater than 30% of an inner diameter of the inversionsupport catheter, and wherein a second region of the knitted tubeadjacent to the second end has an expanded outer diameter that is lessthan the expanded outer diameter of the first configuration; pulling thepuller proximally within the inversion support catheter to roll theknitted tube over the distal end of the inversion support catheter sothat the knitted tube inverts over a distal end of the inversion supportcatheter, driving the loop stitches outward from the kitted tube bybetween 0.5 and 10 mm; capturing the clot with the knitted tube; andpulling the clot proximally into the inversion support catheter.

These methods may also include sliding the second end along the lengthof the inversion support catheter when pulling the puller proximally,wherein the second end comprises a cuff having a stiffness that isgreater than a region of the knitted tube adjacent to the cuff.

Any of these methods may include limiting travel of the knitted tube sothat the second end does not roll and invert over the distal end of theinversion support catheter when pulling the puller proximally.

In general, advancing may comprise advancing over a guidewire.

Expanding of the flexible tube (e.g., knitted tube) may compriseexposing the knitted tube from out of an intermediate catheter, whereinthe inversion support catheter is within a lumen of the intermediatesupport catheter.

BRIEF DESCRIPTION OF THE DRAWINGS

The features and aspects of the various embodiments of the disclosedinventions are set forth with particularity in the claims that follow. Abetter understanding of the features and advantages of the presentinvention will be obtained by reference to the following detaileddescription that sets forth illustrative embodiments, in which theprinciples of the invention are utilized, and the accompanying drawingsof which:

FIG. 1A illustrates one example of a delivery catheter (“intermediatecatheter” or I.C.) that may be used with a mechanical thrombectomyapparatus as described herein.

FIGS. 1B-1C2 illustrate components of a mechanical (e.g., invertingtractor) thrombectomy apparatus; FIG. 1B shows an example of an elongateinversion support catheter that is configured to include a plurality ofslots (shown here as transverse slots) arranged along the catheter inorder to enhance flexibility of the elongate inversion support catheterwhile providing sufficient column strength to resist buckling as thetractor tube is drawn proximally to invert. The slot pattern of FIG. 1Bis intended as a single example only. Other slot/cut-out patterns may beused. FIGS. 1C1 and 1C2 show a tractor tube inverted (e.g., in aninverted configuration) over a puller; in FIG. 1C1 the puller is apuller catheter (PMC) while in FIG. 1C2 the puller is a guidewire. Thetractor tube is shown schematically and may be a knitted, woven, orbraided material.

FIGS. 2A-2C illustrate the operation of an inverting tractor mechanicalthrombectomy apparatus as described above. FIG. 2A shows the assembledapparatus in which the tractor tube is coupled to the puller and withinthe elongate inversion catheter with the tractor tube inverting over thedistal end of the elongate inversion catheter. FIG. 2B shows theapparatus of FIG. 2A delivered within a vessel near a clot. FIG. 2Cshows the operation of the apparatus to withdraw the clot by pullingproximally on the tractor tube from within the elongate inversionsupport catheter so that the tractor tube is pulled to roll over andevert from the inverted configuration on the outside of the distal endof the elongate inversion support catheter into the un-invertedconfiguration within the elongate inversion support catheter, pullingthe clot with it.

FIG. 2D illustrates an example of a tortious path that the invertingtractor mechanical thrombectomy apparatus may have to navigate in orderto reach the clot.

FIG. 3A is an example of a preloaded assembly of an inverting tractormechanical thrombectomy apparatus within an intermediate catheter thatmay be used as described in order to deliver an inverting tractormechanical thrombectomy apparatus though a tortious vessel to adeployment location. In this example, the elongate inversion supportcatheter is held within the intermediate catheter (and may be locked inposition) until deployed, while the pusher (e.g., PMC) and tractor arepartially extending distally. A guidewire may also be used. FIG. 3B showa prototype assembly (pre-assembled) similar to that shown in FIG. 3A.

FIG. 4A is another example of a preloaded assembly of an invertingtractor mechanical thrombectomy apparatus within an intermediatecatheter that may be used as described in order to deliver an invertingtractor mechanical thrombectomy apparatus though a tortious vessel to adeployment location. In this example, the elongate inversion supportcatheter is extended from the intermediate catheter, and extendsdistally along with the puller (PCM). FIG. 4B show a prototype assembly(pre-assembled) similar to that shown in FIG. 4A. FIG. 4C shows anexample of a preloaded assembly such as the one shown in FIGS. 4A and 4Bnavigating through a model of a tortious vessel. FIG. 4D is anotherexample of a prototype pre-assembled assembly (inverting tractormechanical thrombectomy apparatus) such as the one shown in FIG. 4A.

FIG. 5A is another example of a preloaded assembly of an invertingtractor mechanical thrombectomy apparatus within an intermediatecatheter that may be used to deliver an inverting tractor mechanicalthrombectomy apparatus though a tortious vessel to a deploymentlocation. In this example, the elongate inversion support catheter, andthe tractor tube are held within the intermediate catheter, and thedistal end (extending beyond the attachment to the tractor tube) of thepuller extends distally. FIG. 5B show a prototype assembly(pre-assembled) similar to that shown in FIG. 5A.

FIG. 6 is an example of a non-over-the-wire variation of an invertingtractor mechanical thrombectomy apparatus in which the puller is aguidewire, similar to the variation shown in FIG. 2C2.

FIGS. 7A-7C illustrate one example of an inverting tractor mechanicalthrombectomy apparatus in which the apparatus is configured for deliveryof the tractor tube within the elongate inversion support catheter sothat it may later be deployed (as illustrated in FIGS. 7A-7C) to movethe tractor tube portion so that it is inverted over the elongateinversion support catheter distal end.

FIGS. 8A-8C illustrate another method of deploying an inverting tractormechanical thrombectomy apparatus (where the apparatus is configured fordelivery of the tractor tube within the elongate inversion supportcatheter) so that the tractor tube portion is inverted over the elongateinversion support catheter distal end when at the deployment region nearthe clot. In both FIGS. 7A-7C and 8A-8C, withdrawing the tractor tubeinto the elongate inversion support catheter may prevent it fromapplying a compressive force on the elongate inversion support catheteras it is deployed through the vessel, either with an intermediatecatheter or without an intermediate catheter.

FIGS. 9A-9K illustrate one method of delivering and deploying aninverting tractor mechanical thrombectomy apparatus pre-loaded into anintermediate catheter such as the one shown in FIGS. 3A-3B. Similarmethods may be employed to deliver the pre-loaded variations shown inFIGS. 4A and 5A.

FIGS. 10A-10D illustrate another example of a method of delivering anddeploying an inverting tractor mechanical thrombectomy apparatuspre-loaded into an intermediate catheter such as the one shown in FIGS.3A-3B.

FIGS. 11A-11C illustrate a method of using an inverting tractormechanical thrombectomy apparatus to remove clot after the tractor tubeportion of the inverting tractor mechanical thrombectomy apparatus hasbeen completely withdrawn into the elongate inversion support catheter.

FIG. 12A illustrates an inverting tractor mechanical thrombectomyapparatus configured to prevent the tractor tube from retracting fullyinto the elongate inversion support catheter. In FIG. 12A the tractortube has a distal end region that is non-compliant and configured sothat it cannot invert over the distal end of the elongate inversionsupport catheter.

FIG. 12B shows an example of a cuff on the distal end of an invertedflexible tube.

FIG. 13A shows a knitted tractor tube extending in an invertedconfiguration over the outside of a distal end of an elongate inversionsupport catheter. FIG. 13B shows the knitted tractor of FIG. 13Aapplying compressive force to the elongate inversion support catheterwhen the apparatus is advanced distally. FIG. 13C illustrates aninverting tractor mechanical thrombectomy apparatus configured to holdthe kitted tractor tube in a compressed state (in which the transverselyarranged, or approximately transversely arranged loops forming the knitoverlap over more than 20% or their longitudinal length).

FIGS. 14A-14D illustrate examples of inverting tractor mechanicalthrombectomy apparatuses (e.g., elongate inversion support catheterportions) including a stop that is configured to hold the knittedtractor tube in a compressed configuration. In FIG. 14 a polymer stropis shown. In FIG. 14B a Nitinol braid stop has exposed filaments(“fingers”) that prevent proximal sliding of the tractor tube. FIG. 14Cshows another example of a Nitinol braid stop has exposed filaments(“fingers”) that prevent proximal sliding of the tractor tube. FIG. 14Dshows a Nitinol knit segment configured as a stop to prevent proximalsliding of the tractor tube during delivery.

FIGS. 15A-15G illustrate examples of finger-like stop elements similarto those shown in FIGS. 14B-14C. The distally-directed prongs, filamentsor fingers of the stops shown may be placed anywhere along the length ofthe outer surface of the elongate inversion support catheter to preventcompression of the knitted tractor tube during delivery and deployment.

FIG. 15H is another example of a stop on the outer surface of andelongate inversion support catheter having distally-facing prongs thatprevent proximal movement of a woven tractor tube, in order to preventcompressive forces on the elongate inversion support catheter.

FIGS. 16A and 16B illustrate examples of annular housings (“garages”)for the tractor tube on the outer surface of an elongate inversionsupport catheter that may also maintain the tractor tube in a compressedconfiguration on an outer surface of the apparatus, preventing it fromapplying compressive force on the distal end of the elongate inversionsupport catheter. In FIG. 16A, a 48-end braid forms an annular garagefor holding the end of the tractor tube so that it remains in acompressed configuration along the outer surface of the elongateinversion support catheter. In FIG. 16B, the apparatus includes a 10 mmlong braided region (similar to that shown in FIG. 15A, housing the endof the knitted tractor tube and preventing it from extending proximallyand applying compressive forces on the distal end of the elongateinversion support catheter.

FIG. 17 is an example of one variations of an elongate inversion supportcatheter having a high column strength in compression, but a highflexibility when not under compression. In FIG. 17, the elongateinversion support catheter includes a plurality of slots or cut-ourregions arranged approximately transverse to the elongate length (e.g.,long axis). Any of these devices may also include a marker (e.g.,platinum, or other radiopaque material) allowing visualization of thedistal end region of the elongate inversion support catheter.

FIGS. 18A-18J illustrate a method of removing a clot from a vessel asdescribed herein, in which a vacuum (suction) may be applied through thepuller to make and confirm initial contact with the clot. In FIG. 18A,the apparatus is distally advanced over a guidewire adjacent to theclot. The apparatus may initially be in a tracking configuration asshown and discussed, in which the outer (inversion support) catheter isretracted into the lumen of the intermediate catheter while the puller(puller catheter) with the attached flexible tube extending proximallyfrom the distal end, is tracked over the guidewire. In FIG. 18B, theapparatus is changed to a clot-grabbing configuration in which theinversion support catheter is extended towards the distal end of theapparatus, though still proximal to the puller distal end. Theintermediate catheter may also optionally be withdrawn proximally, asshown in FIG. 18C, which in some variations (not shown in FIG. 18A-18J)may allow the flexible tube to expand outwards. FIG. 18C1 shows anexample of a prototype device corresponding to FIG. 18C. Once inposition, suction may be applied through the puller catheter, as shownin FIG. 18D. This focal suction may be applied while advancing theapparatus distally to engage the clot, as shown in FIG. 18E. Theguidewire may be left in place or optionally removed (as shown in FIGS.18D-18E). Once engaged with the clot at the distal end of the puller,which may be detected by observing the flow and/or pressure through thepuller from the suction, the puller may be drawn proximally and/or theinversion support catheter may be moved distally so that the flexibletube rolls over the distal end opening of the inversion supportcatheter. In FIG. 18F approximately 30% of the clot has been drawn intothe inversion support catheter by rolling the flexible tube; in FIG.18G, more, but not all (e.g., approximately 70%) of the clot has beeningested, though a substantial amount of clot remains outside of theinversion support catheter and flexible tube. The vacuum may be left on,or it may be turned off while pulling the puller proximally toengulf/grab the clot. Heavy arrows indicate movement of the componentsof the apparatus, such as the intermediate catheter, which may beadvanced distally, the inversion support catheter, which may also beadvanced distally, and the puller, which may be withdrawn proximally.These motions may be coordinated by the handle (not shown) and/orperformed manually by the user. Once the flexible tube has reached thedistal end of the inversion support catheter, it may stop or be stopped,to prevent it from rolling over the distal end. In FIG. 18A-18J thesecond end of the flexible tube includes a cuff that may prevent theflexible tube from rolling over the distal end when pulling proximallyon the puller, as shown in FIG. 18H. In FIG. 18I, the intermediatecatheter is shown advancing distally beyond the cuff and distal end ofthe intermediate support catheter, which inverts the cuff over andagainst the clot without breaking or disrupting the clot. A vacuum(suction) through the intermediate catheter is also shown being applied(by the small arrows). As shown in FIG. 18J, the flexible tube, pullerand inversion support catheter are then drawn proximally into theintermediate catheter along with the un-engulfed portion of the clot,either by driving the intermediate catheter distally over them, and/orby pulling the inversion support catheter (which may be pulled with thepuller) proximally.

FIG. 19 illustrates an example of a mechanical thrombectomy apparatushaving a knitted flexible tube that is configured to operate even inlarger-dimeter vessels (having proportionally larger-diameter clots) byconfiguring the stitch length of the knitted tube to help grablarger-diameter clots.

FIG. 20A illustrates a larger-dimeter clot (e.g., shown in the top as a15 mm OD, 5 cm long clot) that was captured using a narrower-diametermechanical thrombectomy apparatus having a knitted flexible tube portion(shown having an expanded outer diameter of 5 cm with an 8F inversionsupport catheter). The removed clot is shown on the bottom above theruler.

FIG. 20B shows a side view of a distal end region of a similarmechanical thrombectomy apparatus having a knitted flexible tube thatinverts into a 3 mm inversion support catheter. The knitted flexibletube has a 6 mm expanded first configuration, but may remove clotshaving an outer diameter much larger (e.g., a 15 mm outer diameter clot,as shown in FIG. 20A).

FIG. 21A illustrates and example of a relationship between the length offlexible tube required for a mechanical thrombectomy apparatus asdescribed herein in order to completely engulf (“eat”) a clot having anouter diameter of 15 mm and a length of 5 cm. In this example, theflexible tube is a knitted or woven tube formed of heat-set 0.01 inchNiTi wire.

FIG. 21B shows example of the distal ends of mechanical thrombectomyapparatus tested in FIG. 21A, showing variations with 8 mm expandedouter diameter, 5 mm expanded outer diameter, and 3 mm outer diameter,as well as an 8 French (8F) inversion support catheter.

FIG. 22A shows another example of a cuff that may be at the second endof a flexible tube of a mechanical thrombectomy apparatus. In FIG. 22A,the cuff includes a plurality of slits that may engage with theintermediate catheter (IC) when it is driven distally past the cuff todrive the cuff to invert over the distal end of an inversion supportcatheter, as shown in FIG. 18I, controllable preventing inversion whenpulling the puller, but allowing inversion without disrupting the clotwhen advancing the intermediate catheter, as illustrated in FIG. 22B,showing inversion of the cuff after driving the intermediate catheterdistally.

FIGS. 23A-23B illustrate example of the proximal end of a mechanicalthrombectomy apparatus, showing the components of the apparatus (e.g.,guidewire, inner/inversion support catheter, puller, and intermediatecatheter). FIG. 23B shows another example, of a proximal end of themechanical thrombectomy apparatus showing manual controls, includingvacuum attachment ports, for the different regions.

FIGS. 24A-24B illustrate another example of a set of proximal endcontrols for a mechanical thrombectomy apparatus. In FIG. 24A theapparatus control region is shown in a first puller position (prior topulling the clot in). In FIG. 24B the apparatus control region is shownafter pulling the clot (showing the puller hub extended proximally).

FIG. 25 illustrate an example of a mechanical thrombectomy apparatus inwhich the flexible tube is configured to cut tissue as it rolls into theinversion support catheter. In this example, the flexible tube is aknitted tube that includes sharp cutting edges that may be used to cutthrough tissue.

FIGS. 26A-26B illustrate two exemplary side perspective views ofmechanical thrombectomy apparatuses. In FIG. 26A, similar to that shownin FIGS. 18A-18J, the apparatus include a flexible (e.g., knitted) tubethat is attached at the first end to a puller catheter and is configuredto expand within the inversion support catheter to an outer diameterthat is greater than 40% (shown here, it's greater than 90%) of theinner diameter of the inversion support catheter, driving the region ofthe flexible tube within the inversion support catheter against thewalls, even when unloaded by clot. The other region (un-inverted) of theflexible tube along the outer diameter of inversion support catheter isshown as snug with the inversion support catheter in the un-constrainedconfiguration. This results in the Y-shaped distal profile, for theinverting flexible tube, which may help grab even larger diameter clots.

FIG. 26B illustrates another example of a mechanical thrombectomyapparatus in which the expanded outer profile of the flexible tube isexpanded beyond the outer diameter of the inversion support catheternear the first end where it attaches to the puller, but the second end,that is freely sliding over the inversion support catheter, has a muchsmaller (nearly snug) expanded diameter. This region may also oralternatively include a cuff as described herein.

FIGS. 27A-27C illustrate operation of a mechanical thrombectomyapparatus having a cuff on one end of the flexible tube.

FIGS. 28A-28C illustrate one example of a mechanical thrombectomyapparatus that includes a cuff retainer that may aid in re-sheathing theapparatus into an intermediate catheter.

FIGS. 29A-29C illustrate another example of a mechanical thrombectomyapparatus that includes a cuff retainer.

FIGS. 30A-30C illustrate another example of a mechanical thrombectomyapparatus that includes a cuff retainer.

FIGS. 31A-31C illustrate another example of a mechanical thrombectomyapparatus that includes a cuff retainer (configured as a stop).

FIGS. 32A-32F illustrate examples of mechanical thrombectomy apparatusincluding a cuff that is adapted at the proximal-facing end to aid inre-sheathing into an intermediate catheter. FIGS. 32A-32C illustratecuffs having a tapered proximal end region. FIGS. 32D and 32E illustratecuffs having angled proximal-facing sides. FIG. 32F is an example of acuff having a proximal stent-like region.

FIGS. 33A-33E illustrate one example of a re-loading mechanicalthrombectomy apparatus in which a single-use sub-assembly (including thepuller, cuff and flexible tube) can be withdrawn and a new sub-assemblyinserted.

FIGS. 34A-34C illustrate operation of a re-usable/reloadable mechanicalthrombectomy apparatus.

FIG. 35 schematically illustrates one example of an ejection apparatusthat may be used to assist in ejecting captured clot material and/orreloading of a mechanical thrombectomy apparatus.

DETAILED DESCRIPTION

In general, described herein are inverting tractor mechanicalthrombectomy apparatus having a tractor tube, configured as an invertingflexible tractor tube that may be pulled proximally to invert over andinto the distal end of an elongate inversion support catheter. An end ofthe tractor tube may be coupled to a puller (e.g., pull wire, pullcatheter, etc.) to provide the proximal pulling force. In particular,described herein are apparatuses and methods of using them that improveor enhance tracking of the apparatus from a patient insertion side(e.g., a femoral region or elsewhere) though a tortious vessel, to adeployment site where the apparatus may be deployed to mechanicallyremove a clot by rolling the tractor tube into the elongate inversionsupport catheter and grabbing the clot.

In general, the apparatus may be adapted to improve tracking bypreventing stiffening or loss of flexibility of the elongate inversionsupport catheter that may otherwise occur when the tractor tube, whichmay extend along a substantial distance proximally from the distal openend of the elongate inversion support catheter, applies a compressiveforce on the elongate inversion support catheter. This may occur, forexample, when the apparatus is deployed through the vessel and/orthrough an intermediate catheter. Although the outer surface of theelongate inversion support catheter, and/or the outer surface of thetractor tube may be lubricated to reduce friction, the distal movementof the apparatus may still result in a drag force on and portion of thetractor tube that is on the outside surface of the elongate inversionsupport catheter. The resulting drag force is transferred to the distalend of the elongate inversion support catheter, resulting in acompressive force on the elongate inversion support catheter. An exampleof this is illustrated in FIG. 13B, described in greater detail below.

This issue may be exacerbated when the apparatus includes an elongateinversion support catheter that is configured to have both a high columnstrength (resisting compression) and an increased flexibility, e.g., byincluding one or more cut-outs, slots, etc. arranged down the length ofthe elongate inversion support catheter. For example, metal tubes (e.g.,Nitinol tubes, etc.) having transversely arranged slots cut into themalong the length of the elongate inversion support catheter may have ahigh column strength, while remaining sufficiently flexible (at least inan unloaded/un-tensioned configuration).

In general, an inverting tractor mechanical thrombectomy apparatus forremoving a clot from a vessel may be a system, assembly or deviceincluding an elongate inversion support catheter (such as thosementioned above), having a distal end and a distal annulus (distal endopening), and a flexible tractor assembly including a flexible tractortube coupled to an elongate puller within the elongate inversion supportcatheter. The flexible tractor tube is configured to roll and invertover the distal end opening of the elongate inversion support catheter.Knitted tractor tubes are of particular interested and described herein,although it should be understood that other tractor tubes, e.g., woven,braided, etc., may be used.

Tracking of any of the inverting tractor mechanical thrombectomyapparatus described herein may include an intermediate catheter (I.C.)as a delivery catheter along with a guidewire. For example, FIG. 1Aillustrates an example of a typical intermediate catheter 101 that maybe used. Note that in some variations, as will be illustrated below, anintermediate catheter is not needed or used and the inverting tractormechanical thrombectomy apparatus may be delivered to the deploymentsite near the clot to be removed without the need for an intermediatecatheter.

FIG. 1B illustrates one example of an elongate inversion supportcatheter. In this example, the elongate inversion support catheter 103is formed of a normally high column-strength material (such as a metal,e.g. Nitinol) having a number of openings (e.g., cut-out regions) orslots along the length to provide enhanced flexibility. The distal endof the elongate inversion support catheter is open 105. Either theentire length or a portion of the length may be cut/slotted asdescribed. The elongate inversion support catheter includes a catheterbody having a distal end region that includes a distal end opening 105.The distal end region may have an increasing softness (measured bydurometer, e.g., shore durometer) except that the very distal-most endregion (distal end 105, including the distal end opening) may besubstantially less soft than the region immediately proximate to it.Thus, although the distal tip region of the catheter (e.g., the distalmost x linear dimensions, where x is 10 cm, 7 cm, 05 cm, 4 cm, 3 cm, 2cm, 1 cm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm) has an increasingsoftness/decreasing harness extending from the proximal to distal ends,the very distal end region 107 (e.g., measured as distal most z lineardimensions, where z is 1 cm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2mm, 1 mm, 0.8 mm, 0.5 mm, 0.3 mm, 0.2 mm, etc., and z is always at leastthree times less than x) has a hardness that is greater than thehardness of the region immediately proximal to it, and may be as hard orharder than the proximal-most region of the distal tip region.

In FIG. 1B, the elongate inversion support catheter is an elongatehollow catheter having a column strength that is sufficient to preventbuckling when the catheter is pulled over the distal annulus (distal endopening). Thus, the elongate inversion support may be configured so thatit does not collapse (e.g., buckle) when 500 g or less of compressiveforce is applied (e.g., able to withstand at least about 500 g, at leastabout 700 g, at least about 600 g, at least about 500 g, at least about400 g, at least about 300 g, etc. of compressive force) forneurovascular applications. For peripheral vascular applications theelongate inversion support may be selected or configured to withstand atleast 1500 g of compressive force (e.g., at least about 2000 g, 1900 g,1800 g, 1700 g, 1600 g, 1500 g, 1400 g, etc. of compressive force). Ingeneral, any of the apparatuses described herein may include an elongateinversion support catheter that is not a full-length catheter, but mayinclude a portion of a catheter, typically at the distal end, connectedto a rod, wire, hypotube, or the like. In FIG. 1B the catheter 103 ofthe elongate inversion support catheter may be any appropriate type ofcatheter or portion of a catheter, including microcatheters appropriatefor neurovascular use.

In some variations the distal end 105 of the elongate inversion supportcatheter is adapted so that the tractor may slide or roll and invertover the distal end of the catheter without being caught (binding,jamming) or without substantial friction. For example, in somevariations the distal tip (end) may be curved or radiused, particularlyon the outer surface (e.g., the transition from outer diameter to innerdiameter).

FIG. 1C1 shows an example of a flexible tractor tube 111 coupled to anelongate puller 113, forming a pullable tractor assembly 140. In thisexample, the tractor tube 111 is shown integrated with the puller 113and extending back over the puller. The puller in this example is acatheter (e.g. a micro catheter, also referred to herein as a PMC orpull micro catheter). In this example, the opposite end of the flexibletractor tube 111 is open and free (e.g., not connected to the puller orcatheter, e.g. elongate inversion support catheter). As will bedescribed in greater detail below, this open, free, end may be adaptedto be expanded and held open, e.g., by shape setting back on itselfand/or by including an annular bias, to enhance deployment andpositioning of the catheter between the flexible tractor tube and thepuller. In FIGS. 1C1 and 1C2, the tractor tube is formed of material(e.g., wove, knitted, braided, etc.) that is flexible and elongate. Thetractor 111 is shown extended from the puller in a first configuration.It may be particularly beneficial if the relaxed outer diameter of theflexible tractor in this first configuration has a greater outerdiameter than the outer diameter of the catheter of the elongateinversion support into which the tractor will be positioned prior toinverting. The flexible and tubular tractor 111 may be sufficiently softand flexible (e.g., having a low collapse strength) so as to easily rolland fold over the distal aperture of the elongate inversion support. Thetractor 111 may be configured, e.g., by shape-setting (heat setting,etc.), to expand in the relaxed first configuration to a radial diameterthat is between 1.1 and 10 times (e.g., between 1.1× and 5×, between1.1× and 4×, etc.) the diameter of the inner diameter of the catheter ofthe elongate inversion support when unconstrained. In FIG. 1C2, thetractor tube 111 is shown coupled to a guidewire (non-hollow structure)115. The tractor may be formed of a mesh, braided, woven, knitted, orsheet of material and is generally adapted to grasp the object to beremoved (e.g., blood clot).

FIG. 2A illustrates an example of an inverting tractor mechanicalthrombectomy apparatus 200 deployed. In FIG. 2B the inverting tractormechanical thrombectomy apparatus is shown deployed near a clot 209. Inthe deployed configuration the puller 201 (shown here as a puller microcatheter) is held within the elongate inversion support catheter so thatthe flexile tractor tube 203 extends from the end of the puller andexpands toward the inner radius of the elongate inversion supportcatheter 207; at the distal end opening of the elongate inversionsupport catheter the tractor tube inverts over itself and extendsproximally in an inverted configuration over the distal end of theelongate inversion support catheter. As shown in FIG. 2C, by pulling thepuller proximally, the tractor tube rolls and everts over the distal endopening of the elongate inversion support catheter, drawing the adjacentclot into the elongate inversion support catheter, as shown.

FIG. 2A the elongate inversion support catheter is positioned betweenthe tractor tube and the puller so that the tractor tube can be pulledproximally by pulling on the puller and rolling the tractor tube intothe elongate inversion support catheter so that it inverts. The portionof the tractor tube that is inverted over the distal end of the elongateinversion support catheter has an outer diameter that is greater thanthe outer diameter of the elongate inversion support catheter. Thetractor is biased so that it has a relaxed expanded configuration with adiameter that is greater than the outer diameter (OD) of the elongateinversion support catheter; in addition, the tractor tube may also beconfigured (e.g., by heat setting, etc.) so that when the tractor tubeis everted and rolled over the distal end opening into the elongateinversion support catheter, the outer diameter of the tractor tubewithin the elongate inversion support catheter has an outer diameterthat is greater than the inner diameter of the elongate inversionsupport catheter (e.g., greater than 0.1×, 0.5× 0.6×, 0.7×, 0.75×, 0.8×,0.9×, 1×, etc. the inner diameter, ID, of the elongate inversion supportcatheter. This combination of an un-inverted diameter of the tractortube of greater than the diameter of the OD of the elongate inversionsupport catheter and an inverted diameter of the tractor tube of greaterthan 0.7× the ID of the elongate inversion support catheter issurprisingly helpful for preventing jamming of the apparatus, both whendeploying the apparatus and when rolling the tractor over the distal endopening of the elongate inversion support catheter to grab a clot. Thetractor may be expandable and may be coupled to the puller as shown. Insome variations the flexible tractor and the puller may comprise thesame material but the tractor may be more flexible and/or expandable, ormay be connected to elongate puller (e.g., a push/pull wire orcatheter).

In FIG. 2C the clot may be drawn into the elongate inversion supportcatheter by pulling the tractor proximally into the distal end of theelongate inversion support catheter, as indicated by the arrows 211,211′ showing pulling of the inner portion of the flexible tractor,resulting in rolling the tractor over the end opening of the catheterand into the catheter distal end and inverting the expandable distal endregion so that it is pulled into the catheter, shown by arrows. The endof the tractor outside of the catheter may be “loose” relative to theouter wall of the catheter.

In general the mechanical thrombectomy apparatuses described herein maybe highly flexible, both before actuating and during operation. Forexample, the flexible tractor may not increase the stiffness/flexibilityof the catheter of the elongate inversion support, and particularly thedistal end region of the catheter too much, to avoid impactingmaneuverability, particularly within tortious vessels of theneurovasculature. Described herein are flexible tractor tube portionsthat increase the stiffness of the last “y” cm (e.g., the distal most 20cm, 18 cm, 15 cm, 12 cm, 10 cm, 9 cm, 8 cm, 7 cm, 6 cm, 5 cm, 4 cm, 3cm, 2 cm, 1 cm, etc.) of the catheter less than a predeterminedpercentage (e.g., less than 10%, 12%, 15%, 18%, 20%, 25%, 30%, etc.).For example, described herein are flexible tractor tube portions thatpass through the catheter and double back over the distal end of thecatheter but increase the stiffness of a distal 5 cm of the catheter byless than 15% of the stiffness of the distal 5 cm of the catheterwithout the flexible tube extending therethrough and doubling back overthe distal end of the catheter.

The tractors may be woven, braided and/or knitted materials. For wovenand braided materials, which may include a plurality of fibers that arewoven or braided to form the inverting tube, these structures may betuned to prevent jamming and/or to reduce the force necessary to pullthe tractor and invert over the catheter tip. For example, themechanical atherectomy apparatus may include a braid-type tractor thatcan roll freely around the tip of catheter even in a tortuous anatomyand when grabbing clot by tuning one or more of the braid structure;minimizing the braid angle; including a hydrophilic coating on thedistal aspect of the catheter outer diameter (OD) or the inner diameter(ID) of the braid (e.g., tractor); including a radiused wall on thecatheter; and/or increasing the stiffness of the distal tip regionrelative to adjacent proximal regions. Alternatively, it may beadvantages to have a hydrophilic coating on 1, 3, 5, 10, or 15 cm of thedistal ID or the entire catheter ID. This may even enhance aspiration ofthe clot without a tractor element.

As mentioned, the tractor (e.g., braided, woven, knitted, etc.) may beconfigured to collapse down into the inner diameter (ID) of the catheteras little as possible. For example the tractor may collapse to an IDthat is greater than, equal to, or within 90%, 85%, 75%, 70%, 65%, 60%,or 50% of the catheter inner diameter (ID)/Catheter Tip OD, since, whenthe tractor is being pulled around catheter tip it may create axialtension on the tractor (e.g., braid, knit, etc.) that can inadvertentlycause the tractor to jam on the catheter tip. When tractor is pulledaround catheter tip, the tractor is being pulled in the axialorientation creating axial tension on tractor structure as the tractoris being pulled through the catheter ID. By having the tractor elementsjam at an ID greater than or equal to 90%, 85%, 75%, 70%, 65%, 60%, or50% of the catheter ID (or in some variations, OD), when being axiallytensioned, the tractor is less likely to grab/synch down onto thecatheter tip, helping the braid roll around the catheter tip with lessaxial force applied by the user. If less axial force is required by theuser to pull the tractor structure around the tip then the catheter tipis less likely to buckle or deflect when retracting the tractor. It maybe advantageous to minimize the chance the catheter tip will buckle. Thetractor can be tuned to “jam” at a specific ID by controlling any of thefollowing variables and in any combination: selecting a specific numberof braid ends, selecting the size/diameter of the braid ends; selectingthe braid material (e.g., multifilament or monofilament); heat settingthe bias on the braid (e.g., braid diameter); and selecting a braidpattern, e.g., 1×2, 1×1 or any other pattern.

The braid angle may be minimized to prevent locking up of the rolling ofthe tractor over the catheter end opening. Typically, the lower thebraid angle (e.g., 45 degrees or less, 40 degrees or less, 35 degrees orless, 30 degrees or less, 25 degrees or less, 20 degrees or less, etc.)the less likely it is to have the braid cross over points catch on thecatheter tip.

In any of the variations described herein, the catheter and/or a surfaceof the tractor may be coated to enhance rolling over the distal endregion of the catheter. It may be helpful to have a hydrophilic coatingon the distal aspect of the catheter OD or the ID of the tractor so thetractor can more easily side over the catheters distal end and aroundthe tip of the catheter when pulled through the inside of the catheter.

The radius wall of the catheter tip may be chosen/set to within a rangethat allows sliding. For example, it may be helpful for the tip of thecatheter to have the largest radius possible but at least 0.025″ radiuswall on the catheter, ideally approximately 0.05″ radius wall.

The stiffness of the distal of the elongate inversion support cathetermay be sufficiently stiff to prevent collapse as the tractor is pulled;it may also be lubricious (e.g., by a coating or material property). Thedistal most section of the elongate inversion support catheter tip(e.g., the last 5 mm) may be fabricated of a material which is stiffenough and lubricious enough so the distal tip of the catheter does notcollapse or buckle inward ward when the braid structure is rollingaround the catheter tip. Thus, the distal tip may have a stiffness thatis greater than the more proximal region at the distal end of thecatheter.

It may be helpful or desirable to have pores in the tractor. A lack ofgaps or small pore size may limit the ability of the braid to grab clot.Alternatively or additionally, it may be desirable to form a braidstructure with texture. One example is to braid two or more differentdiameter braid ends into the same structure: the difference in braid enddiameters will help form a texture to the braid structures outersurface, aiding the grabbing of the clot when rolling the braid-dozeraround the catheter tip.

As an alternative (or in addition) the tractor may be configured to lockso it does not compress in diameter during axial load by adding acoating, laminate or adhesive to the braid at a desired diameter. Addinga thin coating, laminate or adhesive can inhibit the braid elements fromsliding with respect to each other, thereby locking the braid to aspecific diameter. The coating can be applied while leaving the majorityof the pores and pore area substantially open. Examples of thin coatingsinclude urethanes and silicones with and without hydrophilic coatingsand hydrophilic coatings with no tie layer.

As mentioned above, any of the apparatuses described herein may beconfigured to provide enhance delivery of the apparatus though thetortious anatomy of the vessels in order to deploy the apparatuses nearthe clot. For example, FIG. 2D illustrates an example of a tortious path250 that may be navigated by the apparatuses (including in particularthe apparatuses that are pre-loaded into an intermediate/deliverycatheter).

Preloaded Apparatuses

One solution to the problem with tracking of the inverting mechanicalthrombectomy apparatuses such as those described herein, andparticularly those having a high flexibility, high column strengthelongate inversion support catheter (which may stiffen when placed undereven relatively small compressive forces from their distal end by thetractor tube) is to preload the inverting mechanical thrombectomyapparatuses within an intermediate catheter so that a portion of theinverting mechanical thrombectomy apparatus is protected within the bodyof the intermediate catheter, while the rest of the intermediatecatheter portion is advanced over and/or along (with) a guidewire. Forexample, FIG. 3A illustrate one example of a pre-loaded invertingtractor mechanical thrombectomy apparatus for removing a clot from avessel configured to be delivered through a tortious anatomy. In thisexample, the apparatus may include an intermediate catheter 303 having adistal end 305. The intermediate catheter (I.C.) may be considered partof the inverting mechanical thrombectomy apparatus, although in othervariations it may be considered a separate component that is used withthe inverting mechanical thrombectomy apparatus. The apparatus alsoincludes an elongate inversion support catheter 307 (also referred to aspush catheter “880 Device” in FIG. 3) within the lumen of theintermediate catheter. The elongate inversion support catheter 307 has adistal end 311 and a distal end opening. The apparatus also includes apuller 319 extending distally within the elongate inversion supportcatheter and a flexible tractor tube 315 extending proximally from adistal end region of the puller. The puller extends from the distal endof the intermediate catheter and the distal end opening of the elongateinversion support catheter.

In the pre-assembled configuration shown in FIG. 3A, the elongateinversion support catheter is held within the lumen of the intermediatecatheter so that the distal end opening of the elongate inversionsupport catheter is proximal to the distal end opening of theintermediate catheter by a first distance 325. This distance may bebetween about 1 mm and about 10 cm (e.g., between about 2 mm and about10 mm, between about 2 mm and about 20 mm, between about 2 mm and about30 mm, etc.). The elongate inversion support catheter may be fixed inposition relative to the intermediate catheter, so that as the twocatheters move together, until released. For example, the proximal endsof the intermediate catheter and the elongate inversion support cathetermay be removably coupled.

The tractor tube in the pre-assembled apparatus of FIG. 3 extendsbetween the elongate inversion support catheter and the intermediatecatheter for some second distance along the length 323 of the elongateinversion support catheter. Securing the end of the tractor tube betweenthe I.C. and the distal end of the elongate inversion support cathetermay help both hold it in place, so that it may be held in compression,as will be described in greater detail below, which may also helpprevent it from applying compressive force to the distal end of theelongate inversion support catheter. For example, the second length 323may be between about 1 mm and about 50 cm (e.g., between about 5 cm andabout 10 cm, between about 1 cm and about 20 cm, between about 1 cm andabout 10 cm, between about 2 cm and about 20 cm, between about 2 cm andabout 10 cm, etc.).

The portion of the tractor tube 315 and puller 319 (e.g., pull microcatheter, or pmc) in this pre-loaded example may extend distally andride over the guidewire 317. The tractor tube and puller may also belongitudinally fixed relative to the intermediate catheter 303 (e.g., byreleasably locking, e.g., at the distal end region) or they may besomewhat longitudinally slideable (and, in some variations, preventedfrom exceeding a range of, e.g., between about 1 mm and 20 cm from thedistal end opening 305 of the intermediate catheter 303.

In practice, the portion 327 of the tractor tube 315 that extendsoutside of the intermediate catheter 303 may be between about 1 mm andabout 20 cm (e.g., between about 1 cm and about 7 cm, between about 1 cmand about 10 cm, between about 1 cm and about 15 cm, between about 2 cmand about 10 cm, between about 2 cm and about 7 cm, etc.). As mentioned,this distance may be fixed (e.g., by fixing the puller with respect tothe push catheter and/or I.C.), or variable. In any of these variations,the puller may extend some distance 329 beyond the distal attachmentsite for the flexible tractor tube, or the tractor tube may be attachedat the distal end of the puller. The distance from the attachment siteof the tractor tube and the distal end of the puller may be betweenabout 0 mm and about 10 cm, for example (e.g., between about 1 mm andabout 10 cm, between about 1 mm and about 5 cm, etc.).

In variations in which the pre-loaded apparatus is configured with thepuller (and therefore the tractor tube) and/or the elongate inversionsupport catheter fixed relative to the intermediate catheter fordelivery of the apparatus to the clot (e.g., adjacent to the clot), oncein the deployment location, the elongate inversion support catheterand/or puller may be unlocked so that they may move independently of theintermediate catheter. In some variations, the elongate inversionsupport catheter may be unlocked first, so that it can be advanceddistally into the tractor tube and over the puller; once the distal endof the elongate inversion support catheter is near the attachment sitefor the tractor tube on the puller, the puller may be also be released(manually or automatically).

FIG. 3B illustrates another example of a pre-loaded apparatus(pre-loaded inverting tractor mechanical thrombectomy apparatus forremoving a clot from a vessel configured to be delivered through atortious anatomy). In FIG. 3B, the tractor tube is a knit 355 that isbonded to the puller near a distal end region, described in FIG. 3A. Thedistal end region of the puller (pmc) 337 extends from the intermediatecatheter 343. The opposite end 345 of the tractor tube, approximately 1cm) is held between the intermediate catheter and the elongate inversionsupport catheter 341, which is entirely within the intermediatecatheter. Exemplary dimensions are shown by the ruler above theprototype device.

Another variation of a pre-loaded inverting tractor mechanicalthrombectomy apparatus for removing a clot from a vessel configured tobe delivered through a tortious anatomy is shown in FIGS. 4A-4D. In FIG.4A, the apparatus contains the same elements shown in FIG. 3A, but theyare arranged and interact in a different manner. For example, thepre-loaded apparatus includes an intermediate catheter 403 with an opendistal end 405, an inner elongate inversion support catheter 307, atractor tube 415 and a puller 419. In FIG. 4A, he tractor tube isconnected to a distal end region of the puller (e.g., within a fixeddistance 425 of the distal end of the puller, e.g., between about 0 mmand 10 cm (e.g., about 1 mm to about 10 mm, etc.) as in the example inFIG. 3A. The opposite end of the tractor tube is held between theintermediate catheter 403 and the elongate inversion support catheter407, as in FIG. 3A. For example, between about 1 mm and about 50 cm oftractor tube (e.g., between about 5 cm and about 10 cm, between about 1cm and about 12 cm, etc.) may be between the intermediate catheter andthe elongate inversion support catheter; the tractor tube may be heldloosely, or it may be held so that the distal end of the tractor tube onthe outside of the elongate inversion support catheter is compressed, itfrom being pulled distally by friction from the vessel walls, resultingin compressive forces on the distal end of the elongate inversionsupport catheter.

In FIG. 4A, the elongate inversion support catheter is secured inposition relative to the puller so that the distal end opening of theelongate inversion support catheter is near the attachment site for thetractor tube on the puller. For example, the distance between theelongate inversion support catheter distal end opening and theattachment site for the tractor tube 429 may be between about 0 mm andabout 10 cm (e.g., between about 0 mm and about 1 mm, between about 0 mmand about 2 mm, between about 1 mm and about 5 mm, between about 1 mmand about 3 mm, etc.). As discussed above for FIG. 3A, the puller,elongate inversion support catheter and intermediate catheter may bereleasably locked together so that they move together. The portion ofthe puller from the attachment site of the tractor tube to the distalend of the puller 425 may, as described for FIG. 3A, above, be betweenabout 0 mm and about 10 cm (e.g., between about 0 mm and about 7 mm,between about 0 mm and about 5 mm, etc.).

In operation, the pre-assembled apparatus shown in FIG. 4A may advancedistally (e.g., over a guidewire) towards a clot in a vessel with theslightly more flexible distal end portion consisting of a distal portionof the puller, tractor and elongate inversion support catheter extendingdistally from the distal opening of the intermediate catheter by adistance 427 that may be, for example, between about 1 cm and 20 cm(e.g., between about 2 cm and about 7 cm, between about 1 cm and 10 cm,between about 2 cm and about 7.5 cm, etc.). This presents a moreflexible distal end region that tapers slightly over the guidewire,allowing the apparatus to navigate tortious vessels, including thosehaving branches. Once the distal end of the apparatus is within thedeployment region, near (e.g., adjacent to) the clot to be removed, theapparatus may be deployed by removing the coupling between theintermediate catheter, puller and elongate inversion support catheter,and allowing the intermediate catheter to be withdrawn at leastslightly, and for the elongate inversion support catheter to be advancedwhile withdrawing the tractor tube proximally to roll the tractor tubeso that it everts over the distal end opening of the elongate inversionsupport catheter.

FIG. 4B illustrates an example of distal end of a prototypepre-assembled apparatus similar to that shown in FIG. 4A. In FIG. 4B theapparatus is shown over a guidewire 417 with the elongate inversionsupport catheter 407 near the attachment site 433 for the tractor tubeonto the distal end region of the puller; a distal end region of thepuller 431 extends from the tractor tube attachment site to the distalend opening of the puller.

FIG. 4C illustrates tracing of an apparatus 460 such as the one shown inFIG. 4B through a tortious model of a blood vessel 455; the flexibledistal end leads the device in tracking and navigating through thevessel. FIG. 4D illustrates another example of a distal end region of apre-loaded inverting tractor mechanical thrombectomy apparatus forremoving a clot from a vessel, also showing exemplary dimensions. InFIG. 4D, the apparatus is threaded over a movable guidewire 417, andshows a knitted tractor tube 415′ that is attached to the distal endregion of a puller 419; an elongate inversion support catheter 407′ isbetween the tractor and the puller, as mentioned above. This ispre-loaded into an intermediate catheter 403′.

Another example of a pre-loaded inverting tractor mechanicalthrombectomy apparatus for removing a clot from a vessel configured tobe delivered through a tortious anatomy. In FIG. 5A, unlike thevariations shown in FIGS. 3A and 4A, both the elongate inversion supportcatheter 507 and the tractor tube 515 are held (e.g., releasably locked)within the intermediate catheter 503. This may prevent the tractor tubefrom pushing against the vessel wall during tracking, and thereforeprevent compressive force on the elongate inversion support catheterthat may otherwise result in it stiffening. In this example, a portion509 of the puller 519 may extend distally out of the intermediatecatheter, e.g., between about 0 mm to about 30 cm (e.g., between about0.5 cm to about 20 cm, between about 1 cm to about 15 cm, between about1 cm to about 10 cm, between about 1 cm and about 5 cm, etc.). Theattachment site of the tractor tube to the puller may be at or near thedistal opening of the intermediate catheter, or it may be offset by somepredetermined distance 507 (or within a range of distances, e.g.,between about 0 mm to about 10 cm, such as between about 1 cm to about 8cm, between about 0 cm to about 2 cm, etc.). Similarly, the elongateinversion support catheter may be preloaded near the attachment site forthe tractor tube to the puller (e.g., with a distance 505 of betweenabout 0 mm to about 20 cm, preferably between about 0 mm and 10 mm). Theentire length of the tractor tube 503 may be any appropriate length,e.g., between about 1 cm and about 60 cm (e.g., between about 5 cm andabout 30 cm, between about 5 cm and about 10 cm, etc.).

In operation, the apparatus shown in FIG. 5A may be deployed over aguidewire (with the component parts all removably secured together,e.g., at a proximal handle) and advanced distally until it is near theclot. In any of these examples, the guidewire may penetrate the clot orit may stop short of the clot. Thereafter, the intermediate catheter maybe withdrawn proximally and/or the elongate inversion support catheteradvanced distally so that the tractor tube is everted from over thedistal end opening of the elongate inversion support catheter and intothe elongate inversion support catheter. Pulling the puller proximallymay continue to roll the tractor tube, while advancing the elongateinversion support catheter to pull the clot into the elongate inversionsupport catheter as the tractor tube everts.

FIG. 5B illustrates another example of the pre-loaded inverting tractormechanical thrombectomy apparatus shown in FIG. 5A. IN this example,only the distal end of the puller 519′ (referred to herein as the pullmicro catheter or PMC), while the tractor tube attached more proximallyto the PMC remains in the intermediate catheter (I.C.) 503′. In thisexample, the puller 519′ rides over the guidewire 517, and has a lengththat is about 2 and 5 cm.

The examples shown in FIGS. 3A-5B shown above include a puller that isconfigured as a puller micro catheter than may be driven over aguidewire. Any of the variations described herein may instead byconfigured so that the puller is a guidewire, as shown in the example inFIG. 6. In this example the puller 619 is a guidewire and the tractortube 615 is attached at one end to the puller. IN this example, thetractor is attached to the distal end of the puller, but it may beattached more proximally, as described above. The elongate inversionsupport catheter 607 is interposed between the puller and the tractortube, and may be extended distally so that the tractor tube rolls overthe distal end opening of the elongate inversion support catheter whenpulling the puller to capture and remove a clot. In the variations shownin FIG. 6, the puller does not necessarily need to be a movable (i.e.,longitudinally slideable) pull wire, but may be a fixed wire.

As an alternative to the pre-assembled configurations described in FIGS.3A-5B described above, any of the apparatuses described herein may alsoor alternatively be configured to be deployed through an intermediatecatheter that is first deployed (e.g., using a guidewire and one or moreinternal catheters), and left in place; the inverting tractor mechanicalthrombectomy apparatus may then be delivered through the intermediatecatheter.

Some variations an inverting tractor mechanical thrombectomy apparatusfor removing a clot from a vessel configured to be delivered through atortious anatomy are configured for delivery and deployment to remove aclot without needing an intermediate catheter. For example, in somevariations all, or most of, the tractor tube is withdrawn into theelongate inversion support catheter portion of the apparatus. Thus, theouter surface of the apparatus is the outer surface of the elongateinversion support catheter, which may be smooth, and/or lubricated, andtherefore less likely than the tractor tube to provoke a compressiveforce on the distal end region that would otherwise stiffen the elongateinversion support catheter and prevent it from navigating a tortiousvessel. For example, FIGS. 7A-7C show a first example of an invertingtractor mechanical thrombectomy apparatus for removing a clot from avessel configured to be delivered through a tortious anatomy that isconfigured to deliver the apparatus to the deployment site near the clotwith the tractor withdrawn nearly fully into the elongate inversionsupport catheter.

In FIG. 7A, the inverting tractor mechanical thrombectomy apparatus doesnot include (or require) the use of an intermediate catheter, though onemay be used with it (not shown). The apparatus includes an outerelongate inversion support catheter 707 that includes a stop 704 at ornear the distal end. This stop 704 may be a lip, flange, protrusion, orthe like, and may provide a larger diameter region that engages with acomplimentary stop 816 on the end of the tractor tube 715. The oppositeend of the tractor tube is connected to a puller (puller micro catheter719) similar to the variations described above. When delivered to theclot region of a vessel the puller is withdrawn (preferably loosely, toavoid compressive forces on the elongate inversion support catheter), sothat the tractor tube is withdrawn into the elongate inversion supportcatheter except for small portion at the distal end that is preventedfrom rolling into the elongate inversion support catheter by the stop onthe tractor tube engaging with the stop on the elongate inversionsupport catheter. The apparatus may be driven over a guidewire 717, asshown, until it is proximate to the clot. FIGS. 7B and 7C illustrate atwo-step method for deploying the apparatus that may be used. In Thisexample, the apparatus may be deployed by advancing the puller distally(e.g., “pushing” the puller 775), as shown in FIG. 7B. Thus, the tractorportion will be inverted over itself, ahead of the distal end of theelongate inversion support catheter. Thereafter, as shown in FIG. 7C,the elongate inversion support catheter may be advanced distally intothe pocket 777 formed by the inverted tractor tube. The apparatus isthen ready for the puller to be pulled proximally to roll the tractortube back into the elongate inversion support catheter so that it maycapture a clot, and may therefore be positioned against or adjacent tothe clot.

FIGS. 8A-8C show an alternative method of deploying the apparatus shownin FIG. 7A. FIG. 8A is similar to FIG. 7A, showing delivery of theapparatus to the clot over a guidewire 717. The apparatus includes thetractor tube 715 and elongate inversion support catheter 707, whichinclude a stop on one or both of the elongate inversion support catheterand/or tractor tube to engage the distal end of the elongate inversionsupport catheter with the end of the tractor tube. The apparatus may bedelivered with the tractor tube retracted so that it does not tensionthe elongate inversion support catheter. As shown in FIGS. 8B and 8C,once near the clot, the tractor tube may be repositioned outside of theelongate inversion support catheter so that it can be rolled and used tocapture a clot. In FIG. 8B, the elongate inversion support catheter ispulled proximately 851; since the distal end of the elongate inversionsupport catheter is engaged with the tractor tube to prevent it fromsliding off of the end of the elongate inversion support catheter, whenthe elongate inversion support catheter is pulled proximally whileholding the puller in place (or advancing it distally), the tractor tubewill extend out of the elongate inversion support catheter and invert,as shown. Thereafter, as shown in FIG. 8C, the elongate inversionsupport catheter may be advanced distally between the fold formed by theinverted tractor tube, and the entire apparatus advanced distally backto the clot 833, a shown. Once proximate the clot, the puller may bepulled proximally to capture the clot and remove it.

FIGS. 9A-9K illustrate one method of removing a clot using a preloadedassembly of an inverting tractor mechanical thrombectomy apparatuswithin an intermediate catheter, such as the variation shown in FIG. 3A.In general, a method of using any of the preloaded assemblies ofinverting tractor mechanical thrombectomy apparatuses described herein(e.g., in FIGS. 3A-5B), may be delivered over a wire, through a guidecatheter (or a sheath or balloon guide catheter) to a clot fact, e.g.,proximate the clot. The tractor tube may then be aligned so that itwarps around and over the distal end of the elongate inversion supportcatheter and rolls into (everts) the elongate inversion supportcatheter. Once in positioned (against the face of the clot), theelongate inversion support catheter may be pushed distally while pullingproximally on the puller to ingest the clot, until the full length ofthe tractor tube is pulled proximally and rolled into the elongateinversion support catheter, unless the apparatus includes a stop toprevent it from entering the elongate inversion support catheter.Aspiration may be applied through the elongate inversion supportcatheter and/or the puller (when a puller micro catheter is used) toensure that the clot remains in contact with the distal end of theelongate inversion support catheter and tractor. The intermediatecatheter may then be advanced to the distal end of the elongateinversion support catheter (and aspiration may be applied through theintermediate catheter. The elongate inversion support catheter may bewithdrawn proximally through the intermediate catheter while applyingaspiration, which may both ease retraction of the apparatus within theintermediate catheter and may remove any residual clot portions.

For example, in FIG. 9A, the apparatus has been delivered to the regionadjacent to the clot and deployed out of the intermediate catheter 903.The elongate inversion support catheter 907 and puller 919 are advancedtogether distally to the clot 933 face over a guidewire 917. Theelongate inversion support catheter includes a marking 963 that isvisible under, for example, fluoroscopy or other imaging modality. InFIGS. 9A-9K this marking on the elongate inversion support catheter is aband. In FIG. 9B, the elongate inversion support catheter is advanceddistally while simultaneously or sequentially pulling the pullerproximally so that the tractor tube is rolled over the distal endopening of the elongate inversion support catheter and extends slightlywithin the elongate inversion support catheter (shown biased against theinner diameter of the elongate inversion support catheter). The tractorextending out of the elongate inversion support catheter is pushedagainst the clot face. In FIG. 9B, the guidewire has been left in place;alternatively, as shown in FIG. 9C, the guidewire may be removed.Alternatively, or additionally, the intermediate catheter 903 may bewithdrawn proximally, which may fully unsheathe the tractor, includingthe distal end of the tractor. This may permit the tractor tube to rollfreely over the distal end of the elongate inversion support catheter.The intermediate catheter may be locked to the elongate inversionsupport catheter, so that the two catheters move together wile drawingthe puller proximally to roll the tractor tube over the elongateinversion support catheter, as shown in FIG. 9D. In this example,aspiration (e.g., vacuum) may also be applied, e.g., from within thepuller and/or elongate inversion support catheter, which may help therolling tractor to engage with the apparatus, even before rolling thetractor into the elongate inversion support catheter by withdrawing thepuller proximally.

As shown in FIG. 9E, the puller 919 (PMC) may be drawn proximally whilethe elongate inversion support catheter 907 is advanced towards/into theclot. As previously mentioned, the intermediate catheter 903 mayoptionally be advanced with the elongate inversion support catheter(e.g., the two may be coupled together for this portion of the method.This step may be continued to ingest the clot. FIG. 9F shows the clot30% ingested while still rolling the tractor tube into the elongateinversion support catheter (e.g., by pulling on the puller and/orpushing on the elongate inversion support catheter). FIG. 9G shows theclot 80% ingested and rolling into the elongate inversion supportcatheter. By FIG. 9H, the tractor tube has been fully withdrawn into theelongate inversion support catheter. In this example, the marker 963 onthe elongate inversion support catheter aligns with either a marker onthe puller or the puller itself (if it is visible under imaging). FIG.17 shows another example of an elongate inversion support catheter(slotted 1709 to have a high column strength and high flexibility) inwhich the distal end region 1707 is marked with a platinum material tomake it visible when imaging (e.g., with fluoroscopy). In FIGS. 9A-9H,the entire clot (100%) is captured by the tractor tube within theelongate inversion support catheter once the entire tractor tube hasbeen rolled into the elongate inversion support catheter. However, thisis not necessarily the case, as will be described below, in somevariations additional clot may be drawn into the elongate inversionsupport catheter and/or the intermediate catheter by applying acombination of mechanical action (e.g., pulling the clot with theportion captured by the tractor and suction. For example, FIG. 9I showsthe (optional) use of aspiration through the intermediate catheter (andin some cases, the elongate inversion support catheter). The aspirationmay be left on while withdrawing the apparatus proximally, as shown inFIG. 9J. As mentioned, this may remove any remaining clot.Alternatively, or additionally a second apparatus may be installedthrough the intermediate catheter and delivered to the deployment site(with the intermediate catheter left in position. Finally, as shown inFIG. 9K, an angiogram may be performed through the intermediate catheterto confirm that the vessel is opened. If not, additional procedures(e.g., another preloaded assembly of an inverting tractor mechanicalthrombectomy apparatus may be inserted and used to remove clot) may beperformed.

In general, when deploying any of the inverting tractor mechanicalthrombectomy apparatuses described herein, and in particular, thepre-loaded inverting tractor mechanical thrombectomy apparatuses, thedeployment may include the general steps described below. These stepsmay be customized as indicated herein. First, obtaining access withsheath to the patient's common carotid or ICA. Inject contrast throughthe sheath to image the vessel. Before, during or shortly after, on theback table (e.g., where the proximal end of the mechanical thrombectomyapparatus is held/prepared), flush the intermediate catheter (I.C.) andconnect it to a first rotating hemostatic valve (RHV A), then introducethe elongate inversion support catheter (“880 Device”), puller andtractor through RHV A, e.g., using a peel-away sheath. The elongateinversion support catheter may then be positioned relative to the I.C.,e.g., within about 1 cm proximal to the tip of the I.C., as shown inFIG. 3A, and locked in position relative to the I.C. RHV A may then betightened. A second RHV (e.g., RHV B) may be coupled to the pusher andflushed, and RHV A may be flushed as well. Flush lines may be connected.A guide wire may be loaded through the apparatus. The puller may belocked in position (e.g., as shown in FIG. 3A, extending approximately 1cm or more from the distal end opening of the I.C.) for tracking.

The apparatus may then be tracked to the desired location (e.g., nearthe clot). Once in position, the apparatus may be used to perform thethrombectomy. For example, RHV A and B may be loosened. The couplingbetween the elongate inversion support catheter and the I.C. may bereleased, as may any coupling between the puller and the I.C. and/orelongate inversion support catheter. The elongate inversion supportcatheter may be advanced over the puller until its distal end meets thedistal connection between the tractor tube and the puller. The I.C. maybe pulled back to unsheathe the tractor tube. The elongate inversionsupport catheter and I.C. may again be locked in position relative toeach other. RHV A may be tightened, and the elongate inversion supportcatheter may be advanced to the clot face (possible with aspirationthrough the puller). With a slight pressure forward (distally) on thepusher (and/or I.C.), the puller may be pulled slowing proximally toingest the clot. Alignment markers on the elongate inversion supportcatheter and the tractor (e.g., a region at the end of the tractor tubeon the outside of the elongate inversion support catheter, or a regionof the puller) may be monitored to indicate when the tractor tube iscompletely inverted into the elongate inversion support catheter, andthe user may stop pulling proximally on the puller. RHV A may beloosened and the IC may be advanced, with aspiration, over the elongateinversion support catheter, which may remove any excess clot or piecesof clot. The elongate inversion support catheter, puller and tractor maythen be withdrawn proximally through the I.C. The I.C. may remain inposition and contrast applied to again image through the vessel and aTICI score determined.

Another example of the operation of a pre-loaded assembly of aninverting tractor mechanical thrombectomy apparatus is shown in FIGS.10A-10D. For example, in FIG. 10A, the pre-assembled apparatus issimilar to that shown in FIG. 3A, above. The apparatus includes anintermediate catheter 1003 that entirely houses the elongate inversionsupport catheter 1007 during the tracking through the tortious vessel1081. A puller (pull micro catheter 1019) passes through the elongateinversion support catheter, and include a tractor tube (shown as a knittractor tube 1015) extends from an attachment site 1008 approximately 2mm proximal to the distal end of the puller. The opposite end of thetractor tube is held between the elongate inversion support catheter andthe intermediate catheter (within the intermediate catheter). In FIG.10A, the guidewire 1017 has been inserted distally to and through a clot1033, and the pre-loaded assembly of the inverting tractor mechanicalthrombectomy apparatus is locked (e.g., so that the puller extendsdistally a predetermined distance and the elongate inversion supportcatheter is locked relative to the intermediate catheter) and advanceddistally over the guide wire until it reaches the clot face.

In FIG. 10B, the puller distal end is adjacent to the clot face, and thepuller may be locked in position (e.g., at the handle) while theelongate inversion support catheter is unlocked from the intermediatecatheter and advanced distally over the puller and between the gapformed by the tractor tube. In this example, as the elongate inversionsupport catheter is advanced distally, the tractor tube may compress toa compressed/jammed state, particularly when a knit material is used,before the elongate inversion support catheter slides within its innerdiameter. In FIG. 10C, the elongate inversion support catheter isadvanced distally 1068 over the puller (and under the tractor tube)until the distal end of the elongate inversion support catheter isaligned with the clot, as shown. Finally, as shown in FIG. 10D, thepuller may be pulled proximally 1091 while the elongate inversionsupport catheter is pushed distally 1093 to roll the tractor into theelongate inversion support catheter and capture the clot 1033.

As discussed above, in some variations the tractor tube may becompletely rolled into the elongate inversion support catheter before aclot has been completely removed. In such cases, it may be helpful toensure that the clot is not ripped or fragmented during the process. Inorder to prevent this, the apparatus may be adapted to limit themovement of the puller and/or the tractor, in addition to (or insteadof) using the vacuum and intermediate catheter, as described above.FIGS. 11A-11C illustrate an example in which the clot is too long forthe tractor tube apparatus to fully engulf. In FIG. 11A, similar to FIG.9H, the clot has been captured by the tractor tube 915, which is shownfully retracted into the elongate inversion support catheter 907. Theuser may detect that the tractor tube has been fully retracted becauseeither the puller 919 maybe limited to prevent it moving furtherproximally when the tractor tube is fully retracted into the elongateinversion support catheter. Alternatively, or additionally, the tractortube may include a first marker 963 that may align with a marker on thepuller 965 when the tractor tube is fully retracted, as shown in FIG.11A. Unlike FIG. 9H, however, in this example, the clot has not beenfully captured, and some of it remains outside of the tractor andelongate inversion support catheter.

If the clot is not fully captured by the apparatus, there is a risk thatcontinuing to pull on the clot may disrupt it, e.g., cutting it intofragments. To avoid this, the apparatus may be configured to prevent theuser from continuing to apply force to the clot once the tractor hasbeen fully deployed. As mentioned, the user may be instructed to stopdrawing the puller proximally once one or more markers indicate that thetractor tube has been retracted to a predetermined position. Inparticular, it may be beneficial to prevent the tractor tube from fullyinverting over the tractor tube, as described in FIG. 12A, below.

In some variations, the apparatus may include a stop (e.g., in a handleregion) preventing or limiting the puller to prevent it from extendingbeyond a predefined limit. For example, the limiter or puller stop maybe configured as a physical stop on the puller portion of a handle thatlimits the travel of the puller.

FIGS. 11B-11C illustrate a method for handling this situation withouttearing (and risk harming the patient). In FIG. 11B the elongateinversion support catheter is stopped from advancing any furtherdistally, and instead the intermediate catheter may be advanced distally(with or without aspiration through the intermediate catheter). In FIG.11C, the clot, including the portion outside of the elongate inversionsupport catheter, has been fully captured within the intermediatecatheter, as shown.

FIG. 12A illustrates another example of a configuration of the apparatus(and in particular the tractor tube) in which the distal end of thetractor tube is configured with a non-compliant material 1205 (e.g., acuff) so that it cannot flip or roll over the distal end of the elongateinversion support catheter. This may prevent the user from pulling thetractor all the way around the catheter. In some variations, the cuff isconfigured to permit the tractor tube to flip over the distal end of theelongate inversion support catheter. For example, a cuff on the outerend of the tractor tube may include one or more slits (e.g., between oneand 20 slits or slots) extending along its length configured to permitit to flip and invert, but providing an increase in the stiffness of thetractor tube. In any of these variations, the cuff on the outer end ofthe tractor tube may include a marker (e.g., radiopaque material); forexample, the cuff may be a polymer including a platinum or otherradiopaque material suspended in it. FIG. 12B illustrates an example ofa cuff 1205′ at one end of a flexible tube (‘tractor’) 1207 that hasbeen inverted over the inversion support catheter 1209.

As mentioned above, any of these apparatuses may include one or morefeatures that may be used to improve tracking, and in particular, bypreventing the elongate inversion support catheter from stiffening. Thismay be a problem with the high column-strength, highly flexible elongateinversion support catheters that include one or more slot or cut-outregions along their length. One feature that may be included, discussedabove, is the use of configurations in which the tractor tube, andparticularly knitted tractor tubes, are delivered in a compressed state,rather than a stretched state. As mentioned above, pinning one end ofthe tractor tube in the intermediate catheter may be configured to dothis in some of the preloaded configurations described above. FIGS.13A-16B illustrate other variations. For example, FIG. 13A shows aknitted tractor tube 1315 over an elongate inversion support catheter1307 that is stretched. The woven links are connected end-to-end(forming a helical winding pattern around the elongate inversion supportcatheter). FIG. 13B illustrates the resulting compressive load on thecatheter tip in this configuration; friction loads on the knit duringtracking may pull on the distal end of the elongate inversion supportcatheter, causing it to stiffen in compression. However, suchcompressive loads may be lessened or eliminated by using a wovenmaterial held in a compressed configuration, as shown in FIG. 13C. Inthis example, the interlocking loops forming the weave are overlappingin a compressed state.

This compressed state may be maintained by pinning, securing or holdingone or more ends or lengths of the tractor tube in place when thetractor tube is compressed. Any appropriate mechanism for holding thecompression may be used. For example, the apparatus may include a stopor lock to engage with one or more regions of the tractor tube and holdit in a compressed configuration during tracking. FIGS. 14A-14Dillustrate variations of structures (stops) that may be used to hold thewoven tractor tube on the outside of the elongate inversion supportcatheter in a longitudinally compressed state. In FIG. 14A, the elongateinversion support catheter includes a polymeric lip, ridge or rim (stop)1401 that may secure one end of the woven tractor tube against theelongate inversion support catheter with the tractor tube incompression. Distal force may be applied to pull the tractor tube out ofthe stop (not shown). FIG. 14B shows a Nitinol (NiTi) braid 1403 thatholds the knitted tractor tube in compression along the length of theelongate inversion support catheter. FIG. 14C shows a similar NiTibraids with exposed ends that engage with the knit of the tractor. FIG.14D a NiTi knit segment also includes projections that engage with theknit, as shown.

FIGS. 14A-14G show similar finger-like elements that may be used toengage with the knit (the loops formed by the knit) of the tractor. InFIG. 15A. the loose ends of the woven material form short “fingers” thatare exposed and engage with the knitted tractor, as shown in FIG. 15B.In FIG. 15C, as similar construction having longer “fingers” of looseends is shown, and FIG. 15D shows the fingers engaging with the knittedtractor tube. FIG. 15E shows “fingers” formed by the loose ends of theweave located approximately 1 cm from the tip of the elongate inversionsupport catheter, and FIG. 15F shows these elements engaging the knittedtractor tube. FIG. 15G is another example of a set of fingers formed ofprojecting metal wires that may be used to removably hold the tractortube against the elongate inversion support catheter in compression.FIG. 15H shows an example of a variation formed by a metal wire havingvery long “fingers”, engaged with a knitted tractor tube, holding it incompression.

Alternatively, or additionally, any of these apparatuses may include ahousing or garage that may be used to hold the knitted tractor tube incompression. For example, FIGS. 16A and 16B illustrate one example ofthis configuration, in which a housing (‘garage’) region 1602 formed ofa 48-end braided material, is used to hold the knitted tractor tube 1604in a compressed state at one of its ends on the elongate inversionsupport catheter. FIG. 16B shows a similar example of a elongateinversion support catheter having a 10 mm long ‘garage’ region made of abraided material 1608.

Removal of Large Clots

Any of the mechanical thrombectomy apparatuses described herein may beadapted to remove large clots. In general, a large clot may be large ineither or both diameter (outer diameter) and length, and may be largerelative to the mechanical thrombectomy apparatus. For example, the clotmay have a diameter that is larger than the diameter of the apparatus(e.g., larger than the expanded diameter of the flexible tube whichcaptures the clot). Thus, the apparatus may be configured to capture andcompress the clot so that it may be withdrawn from the lumen of thevessel, into the lumen of the intermediate catheter and/or inversionsupport catheter. The apparatus may also be configured to capture andremove clots that are longer than the ability of the flexible tube tohold.

In general, FIGS. 18A-18J show a method of removing a clot 1815 from avessel 1815 as described herein, in which a vacuum (suction) may beapplied through the puller to make and confirm initial contact with theclot. For example, FIGS. 18A-18B illustrate an example of an apparatusthat is preloaded and configured to both track to the clot and to removethe large-diameter clot 1815. For example, in FIG. 18A, the apparatus(mechanical thrombectomy apparatus or inverting tube apparatus) includesan intermediate catheter (IC) 1801, an inversion support catheter(“outer catheter”) 1803 within a lumen of the intermediate catheter, apuller (shown as a puller catheter) 1805 within a lumen of the inversionsupport catheter, and a flexible tube (e.g., knit tube) 1809 extendingover the inversion support catheter. The flexile tube has a first end1826 coupled at a distal end region of the puller and a second end 1824comprising a cuff 1825 that is less flexible that a region of theflexible tube adjacent to the cuff, wherein the flexible tube isconfigure to be pulled proximally into the inversion support catheter bypulling the puller proximally so that the flexible tube rolls andinverts over a distal end of the inversion support catheter 1823. Theapparatus is shown over a guidewire 1807. In this example, multipleregions include markers that may be visualized, e.g., under fluoroscopy.For example, the end of the inversion support catheter includes a marker1823, as does the distal end of the puller 1826. The puller may alsoinclude an intermediate marker 1821, shown aligned with the cuff 1825;the cuff also includes a marker. The assembly is shown within the vessel1813.

The apparatus may be distally advanced over the guidewire and positionedadjacent to the clot 1815. The apparatus may initially be pre-loaded ina tracking configuration, in which the outer (inversion support)catheter 1803 is retracted into the lumen of the intermediate catheter1801 while the puller (puller catheter 1805) with the attached flexibletube 1809 extending proximally from the distal end 1826, is moveddistally to track over the guidewire. In FIG. 18B, the apparatus isadjusted into a clot-grabbing configuration in which the inversionsupport catheter 1803 is extended distally towards the distal end of theapparatus, although it is still positioned proximal to the puller distalend 1827. The intermediate catheter 1801 may also optionally bewithdrawn proximally, as shown in FIG. 18C, which in some variations mayallow the flexible tube to expand outwards (see, e.g., FIG. 26B).

FIG. 18C1 shows an example of a prototype device corresponding to theapparatus configured as shown in FIG. 18C. In this example the flexibletube is a woven flexible tube 1809 that is shown extending distally fromthe distal end face 1827 of the puller. The puller is shown over aguidewire 1807.

Once the apparatus is in position near the clot, suction may be appliedthrough the puller catheter, as shown in FIG. 18D. This focal suction(aspiration) 1840 may be applied while advancing the apparatus distallyto engage the clot, as shown in FIG. 18E. In some variations, theguidewire is left in place (not shown) or it may be optionally removed(as shown in FIGS. 18D-18E). Once the distal-facing end of the puller isengaged with the clot, as shown in FIG. 18E, connection to the clot maybe detected by observing the flow and/or pressure through the pullerfrom the suction 1840′. Thereafter, the puller may be drawn proximallyand/or the inversion support catheter may be moved distally so that theflexible tube rolls over the distal end opening of the inversion supportcatheter (these motions are shown by the large arrows). In FIG. 18F,approximately 30% of the clot has been drawn into the inversion supportcatheter by rolling 1866 the flexible tube. In FIG. 18G, more, but notall (e.g., approximately 70%) of the clot has been ingested, though asubstantial amount of clot remains outside of the inversion supportcatheter and flexible tube. The vacuum may be left on, or it may beturned off while pulling the puller proximally to engulf/grab the clot.Heavy arrows indicate movement of the components of the apparatus, suchas the intermediate catheter, which may be advanced distally, theinversion support catheter, which may also be advanced distally, and thepuller, which may be withdrawn proximally. These motions may becoordinated by the handle (not shown) and/or performed manually by theuser. Once the flexible tube has reached the distal end of the inversionsupport catheter, it may stop or be stopped, to prevent it from rollingover the distal end. Rolling of the second end of the flexible tube overthe inversion support catheter distal end may cut or break the clot off,which may be highly undesirable, as it may potentially release the clot,resulting in complications, and/or may require additional removal steps.

In FIG. 18A-18J the second end of the flexible tube includes a cuff 1825that may prevent the flexible tube from rolling over the distal end whenpulling proximally on the puller, as shown in FIG. 18H. In FIG. 18I, theintermediate catheter is shown advancing distally beyond the cuff andthe distal end of the intermediate support catheter. In thisconfiguration (as also described in FIGS. 22A-22B) the motion of theintermediate catheter 1801 may invert the cuff 1825 over the distal endof the inversion support catheter 1803 and against the clot 1815 withoutbreaking or disrupting the clot. A vacuum (suction) may be appliedthrough the intermediate catheter is also shown in FIG. 18I (by thesmall arrows). In FIG. 18J, the flexible tube, puller and inversionsupport catheter are then drawn proximally into the intermediatecatheter along with the un-engulfed portion of the clot, either bydriving the intermediate catheter distally over them, and/or by pullingthe inversion support catheter (which may be pulled with the puller)proximally.

Thus, in the example shown in FIGS. 18A-18J, a larger clot, both indiameter and in length, may be removed by the apparatus.

FIG. 19 illustrates another example of an apparatus that is configuredor adapted to have a smaller diameter (outer diameter) than the vesseland the clot but may be capable of grabbing and removing larger clots(e.g., clots having an outer diameter that are more than 1.5×, more than2×, more than 2.5×, etc.) the outer diameter of the flexible tubecapturing the clot.

In FIG. 19, the apparatus includes a flexible tube that is configured asa knit tube. In this example the region of the knit tube 1901 on theoutside of the inversion support catheter 1903 hugs the outer diameter(OD) of the inversion support catheter. In order to maximize theingesting efficiency/power of the knit when used to capture largerclots, the stich length of the knit may be tuned to the diameter of thevessel in which the apparatus is to be used. For example, in general,the stitch length 1905 is the lateral extent of a loop formed by theknit. In general, the outer diameter 1909 of the inversion supportcatheter may be known, and the inner diameter of the vessel (which maybe equivalent to the outer diameter of the clot) may also be known orapproximated (e.g. from fluoroscopy). Thus, the user, such as a surgeonor physician, may select the appropriate flexible tube (e.g., knit)based on the selected size. For example, in FIG. 19, twice the knit orstich length (knit/stich length) plus the outer diameter of theinversion support catheter may be approximately equal to the ˜Vessel IDin order to maximize power/efficiency when grabbing and/or removingclot. The woven stitches may act as fingers or extensions that swingaround the distal end opening of the inversion support catheter 1907, asshown in FIG. 19. Thus, for vessel inner diameters of between setranges, the knit/stitch length may be determined. In general, theknitted tube may comprise a filament knitted to form a plurality ofinterlocking loop stitches, wherein each loop stitch has a stitch lengththat is between the difference of 25% of the ID and one half the outerdiameter (OD) of the inversion support catheter and 65% of the ID andone half of the OD of the inversion support catheter. For example, twicethe knit/stitch length plus the inversion support catheter OD may beequal to a range of vessel inner diameters (IDs), such as between about90%-110% of the vessel ID, between about 80-100% of the vessel ID,between about 60-100% of the vessel ID, between about 50-100% of theVessel ID, between about 30-100% of the vessel ID, between about 20-100%of the vessel ID, between about 10-100% of the vessel ID, and/or betweenabout 50-130% of the vessel ID.

In practice for most neurovascular and/or peripheral vascularapplications, the knit/stitch length may be between about 0.5 mm andabout 10 mm (e.g., about 0.5 mm, between about 0.1 to 0.5 mm, about 1.mm, between about 0.5-1. mm, about 1.5 mm, between about 1.-1.5 mm,about 2. mm, between about 1.5-2. mm, about 2.5 mm, between about 2.-2.5mm, about 3. mm, between about 3.-3.5 mm, between about 0.5 mm-10 mm(e.g., by any 0.5 mm increment), etc.

In general, the apparatuses described herein may compress a clot. Forexample, FIG. 20A illustrates an example of a clot 2005 shown within thebottle on the top of the figure that is 5 cm long and has an outerdiameter of about 15 mm. A portion of an inverting mechanicalthrombectomy apparatus is shown in the middle of FIG. 20A, showing aninverting support catheter that is an 8 French (8F) catheter 2003 overwhich a flexible tube, formed of a knit material 2001, has beenarranged, including coupling to one end of a puller (not shown). Theflexible (knitted) tube in this example is biased to expand in anuploaded state to an outer diameter than is much greater than the outerdiameter of the inverting support catheter. This apparatus was used toremove the clot 2005, which resulted in compressing the clot 2007, asshown in FIG. 20A, bottom.

Another example of an apparatus for removing clot is shown in FIG. 20B,showing a 10 mm diameter clot 2005′ being grabbed and engulfed by aflexible tube 2001′ having an expanded outer diameter of 5 mm extendingover a 3 mm outer diameter inversion support catheter.

In general, the amount of clot that may be contained (e.g., “eaten”) bythe rolling and inverting devices described herein in a single pass maybe a function of the diameter of the clot, the length of the flexibletube, the structure of the flexible tube (e.g., woven, knitted, etc.)and most importantly, the expanded outer diameter of the flexible tube.For example, FIGS. 21A and 21B illustrate the relationship. In FIG. 21A,the graph shows the length of the flexible tube (e.g., length of thewoven tube, L, needed to fully engulf a clot of 15 mm diameter and 5 cmlength. In general, the results show that for compressible clots, thelength of the flexible tube necessary to fully engulf a 5 cm length of15 mm diameter clot (depending on the type of clot, including itscompressibility) may be between about 6. mm and about 60 mm. Thus, as arough rule of thumb, as much as a 12:1 ratio of flexible tube to clotmay be necessary at this exemplary dimension of a clot. FIG. 21 Billustrates example of different apparatuses 2105 used to generate thedata shown in FIG. 21A.

In general, the knit expands to a larger diameter than the outerdiameter of the catheter once the apparatus is delivered to a clot sitewhen the vessel ID is much larger than the catheter OD. Furthermore, theflexible tube (e.g., knit tube) may expand to a larger diameter than thecatheter once it is delivered to clot site, particularly when the vesselID is much larger than the catheter OD. This is illustrated, e.g., inFIG. 20B. Typically, to maximize the efficiency/power of the flexibletube to ingest a clot, when the catheter is much smaller than the vesselID/clot OD, it may be helpful to have an expanded outer diameter of theflexible tube such that it is at least 10% (e.g., at least 20%, 30%,40%, 50%, 60%, 70%, 80%, etc. of the Vessel ID, or any range between anytwo of these percentages). For example, it may be preferable for theexpanded flexible tube to have at least 30% of the vessel ID. Further,as mentioned above, the expanded diameter of the flexible tube may be atleast about 30%, 50%, 100%, 150%, 200%, 250%, 300%, 400%, 500%, 600%,etc. of the catheter OD (or any range between any of these twopercentages).

As shown in FIG. 19, and discussed above, the extension of the loopstiches in flexible tubes that are knitted (forming “fingers” on theknit, or protrusion that roll and extend beyond the expanded OD of therest of the flexible tube) may further help grab and remove clot. Theseextensions for an apparatus such as shown in FIG. 19 (or 26A) may bebetween about 0.5 mm-10 mm (e.g., between any two value in this range,typically by 0.5 mm increments, including any range between any suchincrements).

FIGS. 22A and 22B illustrate an example of a cuff as discussed above. Inthe example shown in FIGS. 22A and 22B, the cuff 2201 is made of (orincludes) a radiopaque polymer filling the cuff at the second end ofknit tube. This may allow it to be seen under fluoroscopy, and may alsoprevent unraveling of the knitted tube. In FIG. 22A, the cuff includes aplurality of lateral slits 2205 (e.g., four are shown, though 3, 4, 5,6, 7 or more slits may be used). These slits may allow the cuff to flipover inversion support catheter, e.g., when driven by an intermediatecatheter 2203, as shown in FIG. 22B. In this example, the cuff may beformed of a polymer such (e.g., as Pebax 45D+80% tungsten filled). Thecuff may have a wall thickness of less than about 0.025 inches whenlaminated on knit, and may have a length of between 1 and 3 loopstitches (e.g., about 1.5 knit stitches long).

FIGS. 23A-23B and 24A-24B illustrate examples of a proximal end of amechanical thrombectomy apparatus, showing components of the apparatus(e.g., guidewire 2305, inner/inversion support catheter 2307, puller2309, and intermediate catheter 2311. FIG. 23B shows another example, ofa proximal end of the mechanical thrombectomy apparatus showing manualcontrols, including vacuum attachment ports (RHVs) 2317, 2319, for thedifferent regions, as well as the puller hub 2321 at the proximal end.

FIGS. 24A-24B illustrate another example of a set of proximal endcontrols for a mechanical thrombectomy apparatus. In FIG. 24A theapparatus control region is shown in a first puller position (prior topulling the clot in), and includes the inner (e.g., puller) rotatinghemostat valve (RHV) 2417, outer (intermediate catheter) rotatinghemostat valve (RHV) 2419, as well as the puller hub 2421. One or morestop elements 2423, 2423′ may be included on the puller to prevent itfrom pulling and completely inverting the flexible tube over the distalend of the inversion support catheter, as described above; flush ports2432, 2433 are also shown. In FIG. 24B the apparatus control region isshown after pulling the clot (showing the puller hub extendedproximally).

FIG. 25 illustrate an example of a mechanical thrombectomy apparatus inwhich the flexible tube 2505 is configured to cut tissue as it rollsinto the inversion support catheter. In this example, the flexible tubeis a knitted tube that includes sharp cutting edges that may be used tocut through tissue. The apparatus may be used over a guidewire toprevent the cutter from dissecting the vessel wall.

FIGS. 26A-26B illustrate two exemplary side perspective views ofmechanical thrombectomy apparatuses. In FIG. 26A, similar to that shownin FIGS. 18A-18J, the apparatus include a flexible (e.g., knitted) tube2601 that is attached at the first end to a puller catheter 2603 and isconfigured to expand within the inversion support catheter to an outerdiameter that is greater than 40% (shown here as greater than 90%) ofthe inner diameter of the inversion support catheter 2605, driving theregion of the flexible tube within the inversion support catheteragainst the walls, even when unloaded by clot. The other region(un-inverted) of the flexible tube along the outer diameter of inversionsupport catheter is shown as snug with the inversion support catheter inthe un-constrained configuration. This results in the Y-shaped distalprofile 2609, for the inverting flexible tube, which may help grab evenlarger diameter clots.

FIG. 26B illustrates another example of a mechanical thrombectomyapparatus in which the expanded outer profile of the flexible tube 2601′is expanded beyond the outer diameter of the inversion support catheter2605 near the first end where it attaches to the puller 2603, but thesecond end 2621, that is freely sliding over the inversion supportcatheter, has a much smaller (nearly snug) expanded diameter. Thisregion may also or alternatively include a cuff as described herein.

Re-Sheathing the Tractor

Any of the inverting tube apparatuses described herein may be configuredso that the inverting tube apparatus may be retracted (e.g.,re-sheathed) into an intermediate catheter. In particular, any of theinverting tube apparatuses that include a cuff at one end (e.g., at thedistal end) of the inverting flexible tube may be re-sheathed into theintermediate catheter after deployment, including after capturing all ora portion of a clot. FIGS. 27A-27C illustrates operation of an invertingtube apparatus having a cuff on one end of the flexible tube. As shownin FIG. 27A, the inverting tube apparatus includes an inversion supportcatheter 2707, a puller 2705 within a lumen of the inversion supportcatheter, and a flexible tube 2709 extending over the inversion supportcatheter that is coupled at a first (e.g., proximal) end to the puller,and is configured to roll and invert over the open distal end of theflexible inversion support catheter. In some examples, the flexile tube2709 may be a woven or knit material. A second end (e.g., distal) end ofthe flexible tube 2709 may include a cuff 2711 that is less flexiblethat the region of the flexible tube adjacent 2715 to the cuff. In FIG.27A, the apparatus is shown in a deployed or partially deployedconfiguration, in which the flexible tube 2709 and inversion supportcatheter has been extended out of the distal end of an intermediatecatheter 2713, also referred to as a sheath). As discussed above, theapparatus may be delivered to the clot and deployed from out of theintermediate support catheter, including using a guidewire (not shown).

As shown in FIG. 27B, the flexible tube 2709 is configure to be pulledproximally into the inversion support catheter 2707 by pulling 2715 thepuller 2705 proximally so that the flexible tube rolls 2719 and invertsover a distal end of the inversion support catheter; the cuff 2711 mayslide along the outside surface of the inversion support catheter. Asthe device is deployed, the distal end 2714 of the cuff 2711 extendsfurther from the distal end 2715 of the intermediate catheter (sheath2713), which may have a distal end face that faces the deployed cuff2711, se

At any point, either before or after flexible tube has completely, ormostly completely, withdrawn and inverted into the inversion supportcatheter, the apparatus, and in particular the inversion supportcatheter, flexible tube, cuff, and any captured clot material, may bewithdrawn or re-sheathed back into the intermediate catheter 2713.However, in some cases, including (but not limited to) variations havinga cuff 2711 at the second (e.g., distal) end of the flexible andinverting tube 2709 may make it difficult to re-insert the cuff backinto the intermediate catheter, as illustrated in FIG. 27C.

In FIG. 27C, the distal face or end 2717 of the intermediate catheter2713 is shown catching on the distal end 2714 of the cuff 2711 whenattempting to re-sheath the sub-assembly including the cuff 2711,flexible tube 2709 and inversion support catheter 2707 back into theintermediate catheter 2713. Although in some variations this may bedesirable, as it may help push the cuff and end of the flexibleinverting tube off of the end of the inversion support catheter (whichit may further envelop and/or cut the clot, as described above inrelation to FIGS. 18H-18I), in some variations it may be desired toleave the cuff 2711 on an outside of the inversion support catheter2707. In this case, as shown in FIG. 27C, if the distal end 2717 of theintermediate catheter 2713 catches on the end face 2714 of the cuff2711, the cuff may be driven forward, towards the end of the inversionsupport catheter, as shown. In FIG. 17C, this is shown also driving 2725the flexible inverting tube 2709 towards the end of the inversionsupport catheter.

To avoid this, the apparatus may be configured to include one or morecuff retainers that hold the cuff level and/or limit its movement sothat it may slide into the intermediate catheter. FIGS. 28A-28C,29A-29C, 30A-30C, and 312A-31C all describe cuff retainers that may beused.

For example, FIGS. 28A-28C illustrate an example of an inverting tubeapparatus that includes a cuff at one end of the inverting flexible tubeand a cuff retainer, in which the cuff ad flexible tube over theinversion support catheter may be re-sheathed into the intermediatecatheter after deployment. The cuff retainer may facilitate there-sheathing of the cuff and flexible tube into the distal end of theintermediate catheter by applying a force to hold the cuff in a fixedposition on the outside of the inversion support catheter. In somevariations, the cuff retainer may also or alternatively hold the face ofthe cuff level relative to the distal end of the intermediate catheter.

In FIG. 28A, the inverting tube apparatuses include a cuff 2811 on theend of an inverting flexible tube 2809 that inverts into the inversionsupport catheter 2807. A puller (or pusher) 2805 may slide within theinversion support catheter and is attached to the flexible tube 2809.The puller (or pusher) in any of these examples may be a catheter andmay pass a guidewire. The cuff retainer in this example is one or moreleashes or tether 2835 (e.g., a filament, wire, strand, cable, etc.)that is connected at one or more points on the cuff and one or morelocations on the outer surface (or through the outer surface) of theinversion support catheter. The cuff retainer shown is helicallyarranged over the inversion support catheter so that it may be unwoundor unspooled as the puller/pusher pulls and inverts the flexible tubeinto the inversion support catheter. The cuff retainer may be elastic.In some variations the cuff retainer may include multiple tethers thatare spaced circumferentially around the cuff (e.g., spaced equaldistances apart).

The inverting flexible tube sub-assembly (cuff, inverting flexible tube,and inversion support catheter) may be re-sheathed into the intermediatecatheter 2813 after the puller has pulled the flexible tube into theinversing support catheter, so that the cuff has slid over the invertingsupport catheter to a predetermined position 2833 towards the distal endof the inversion support catheter, as shown in FIG. 28B.

Once the cuff retainer 2835 is engaged and applying force against thecuff to hold it in position relative to the inversion support catheter,the intermediate catheter 2813 maybe be slid distally 2850 over thedistal end of the cuff and/or the sub-assembly including the cuff may bedrawn proximally back in to the intermediate catheter. This isillustrated in FIG. 28C.

In the variation shown in FIGS. 29A-29C, the cuff retainer 2935 isconfigured as one or more leashes or tethers 2935 (e.g., filaments,wires, strands, cables, etc.) that is/are attached to a cuff 2911.However, in this example, the cuff retainer passes through an opening2941 in the inversion support catheter 2907 and attaches to the puller(or pusher) 2905. Thus, as the puller 2905 is drawn proximally to pulland invert the flexible tube 2909 into the inversion support catheter2905, the cuff retainer 2935 is also drawn with the flexible tube. Thisconfiguration may coordinate the movement of the puller with themovement of the cuff, as illustrated in FIGS. 29B and 29C. In FIG. 29B.As shown in FIG. 29B the cuff retainer also limits the axial movement ofthe cuff along the outside of the inversion support catheter. Thus, bypulling the puller/pusher 2905 proximally, the cuff retainer may apply aforce holding the cuff in position so that, as shown in FIG. 29C, theintermediate catheter (sheath 2913) may be advanced distally 2971 andover the cuff and outer portion of the flexible tube 2909. Thisconfiguration may also be useful in reloading the flexible tube, as (notshown) force applied to pull the cuff proximally (by pulling/pushing thecuff proximally on the inversion support catheter) may be transmitted tothe puller through the cuff retainer (e.g., the one or more filaments,so that force is applied to both ends of the flexible tube to reload thedevice and also eject any clot within the flexible tube and inversionsupport catheter.

FIGS. 30A-30C illustrate another example of an apparatus including acuff and a cuff retainer 3035, 3035′ in which the cuff retainer includesa pair of leashes or tethers 3035, 3035′ (e.g., filaments, wires,strands, cables, etc.) that are attached to the cuff 3011 and extendproximally through the intermediate catheter 3013 all the way to aproximal end of the device where they may be used to apply force (e.g.,tension) to the cuff. In FIG. 30B, the puller 3005 has been withdrawnproximally 3072 to cause the flexible tube 3009 (attached to the puller)to roll and invert over the distal end of the inversion support tube3007. By securing and/or pulling on the cuff retainer 3035, 3035′, andin some variations also securing and/or pulling on the puller 3005, thecuff may be held in a fixed location while the intermediate catheter3013 is driven distally 3074, as shown in FIG. 30C. In this example, thecuff retainer (e.g., tethers) may be made of a metallic (e.g., stainlesssteel, elgiloy, Nitinol, etc.) or polymeric material. As mentioned, inuse, the cuff retainer may be locked down or free to move (e.g., slide)and may be manipulated by the user near the hub of the inversion supportcatheter or elsewhere on the proximal end of the apparatus.

In some variations, the cuff retainer may be used to pull back thetractor to eject clot after use. For example, the apparatus (e.g., thesup-portion including the cuff, the flexible tube and the puller) may bereloaded on the inversion support catheter and/or material such as aclot captured in the apparatus may be ejected by pulling the cuffproximally (and in some variations pushing the puller/pusher 3005distally).

Although the cuff retainer shown in FIGS. 30A-30C is shown as one ormore tethers, in some examples, the cuff retainer is a tubularstructure, which may be knitted, woven, solid, etc.

In some variations the cuff retainer is a cuff stop near or on a distalregion of the inversion support catheter. For example, in FIG. 31A thecuff retainer is configured as a cuff stop that is formed as a collarattached to the distal end region of the inversion support catheter. InFIG. 31A, the cuff 3111 connected to an end of the flexible tube 3109slides freely along the inversion support catheter 3105, so that whenthe puller/pusher 3105 within the inversion support catheter is drawnproximally 3172 (a shown in FIG. 31B), the cuff may be pulled distallywhile the flexible tube rolls and inverts over the distal end of theinversion support catheter. In FIG. 31B, the cuff is stopped from movingdistally by the cuff retainer 3137 (cuff stop). The intermediatecatheter (sheath 3113) may then be moved distally over the cuff and anyportion of the flexible tube 3109 that is external to the inversionsupport catheter to re-sheath the apparatus, as shown in FIG. 31C.Alternatively, or additionally, the inversion support catheter, cuff,flexible tube and puller may be drawn proximally into the intermediatecatheter. In some variations, a combination of both movements may beused. The puller may be pulled or held so that the cuff is held againstthe cuff retainer while re-sheathing or alternatively the intermediatecatheter (sheath) may drive the cuff against the cuff retainer.

In FIG. 31C the cuff retainer is a stop that is fixed to the outside ofthe inversion support catheter. Any stop that may engage with the outerdistal-facing edge of the cuff and the inversion support catheter may beused. For example, the cuff retainer may be a cuff stop that is a bump,ridge, button, protrusion, band, ring, lip, or the like. One or more(e.g., two, three, etc.) discrete regions arranged around the outside ofthe inversion support catheter may be used. The cuff retainer may madeof any appropriate material, e.g., a polymer or metallic structure, andmay be a solid element or a braid or knit structure.

In addition to these mechanical cuff retainers (cuff stops), electricaland/or magnetic cuff retainers may be used. For example, the cuffretainer may be a magnetic or paramagnetic material that interacts withcuff (which may include a magnetic or parametric material) to limitmovement of the cuff distally.

Any of the cuffs described herein may also include one or more taperedor shaped ends that also help re-sheath the apparatus. For example, insome variations, the proximal end of the cuff may be tapered towards theinversion support catheter.

FIGS. 32A-32C illustrate examples of tapered cuffs that may be used. InFIG. 32A, the apparatus includes a cuff 3211 that has a skived ortapered proximal end 3242. The cuff is attached at the other end to theflexible tube 3209 which inverts and rolls over the inversion supportcatheter 3207 when pulled by the puller 3205 from within the inversionsupport catheter. The sub-assembly including the inversion supportcatheter, flexible (inverting) tube, and the cuff is shown in a deployedconfiguration extending from outside of the intermediate catheter 3213.The tapered cuff may aid in re-sheathing the sub-assembly, including thecuff, back into the intermediate catheter. A tapered cuff may be usedwith or without a cuff retainer, including any of those described above.

FIG. 32B is another example of a tapered cuff 3211 that includes aproximal tapered region 3245′. In this example, the tapered regionincludes serrations that may allow some flexibility of the narrowedproximal end so that it is still free to slide on the inversion supportcatheter. The serrations may be configured as one or more slots, slitsor cut-out regions in the tapered region. The serrations may be limitedto the tapered region.

FIG. 32C is another example of a tapered cuff 3211 having a crown-liketapered region 3255 comprising a number of larger cut-out regions,similar to the serrations of the tapered region in FIG. 22B. In FIG. 32Cthe tapered region may include tapered fingers or projections that maybe triangular, square/rectangular, curved and/or sinuous and/orirregularly shaped tapered extensions. In some variations, the taperedregion is crenelated.

The tapered regions of the cuff may extend over a portion of the cuff,e.g., between 5%-50% of the length of the cuff in the long-axis of theinversion support catheter (e.g., between 10% and 50%, between 15% and50%, between 10% and 40%, etc.). The cuff may be any appropriate length,e.g., between 0.5 mm and 30 mm, between 1 mm and 20 mm, between 2 mm and20 mm, greater than 2 mm, greater than 3 mm, greater than 4 mm, greaterthan 5 mm, greater than 6 mm, etc.).

FIGS. 32D and 32E illustrate cuffs having tapered regions that areangled on the proximal-facing sides. Thus, the proximal-facing side ofthe cuff is angled relative to the body of the cuff and the inversionsupport catheter. In FIG. 32D the cuff 3211 has an angled proximal side3265, but the distal-facing side of the cuff is flat (e.g.,perpendicular to the long axis of the inversion support catheter overwhich it may slide. FIG. 32E shows a cuff 3211″″ that is similar to thevariation shown in FIG. 32D but is also angled on the distal-facingside. The angled proximal-facing side may be tapered (and/or may includetapered cut-out regions/perforations). Cuffs having angled proximalfaces may also be used with a cuff retainer. The angled proximal facemay be formed by cutting the cuff at an angle. Any appropriate angle maybe used, e.g., between 5 degrees and 60 degrees (e.g., between 10degrees and 50 degrees, between 15 degrees and 45 degrees, etc.),measured as the acute angle formed between the proximal-facing side andthe sidewall of the cuff.

FIG. 32F illustrates a cuff 3211 having a proximal-facing stent likestructure 3275 that is low-profile and may also help with re-sheathing.Any of the tapered and/or angled cuffs may also include aproximally-extending stent-like structure. The stent-like structure mayinclude wires, filaments, ribbons, etc. extending from the proximaledge. These sent-like structures may be flattened toward the inversionsupport catheter 3207 outer surface. A stent-like structure may also bereferred to as a low-profile scaffolding, and may extend completely orpartially around the perimeter of the cuff.

Any of the apparatuses described herein may also be configured to bere-loadable. For example, FIGS. 33A-33D illustrate one example of are-loading apparatus in which a single-use subassembly including a cuff3311 (configured as a split cuff), a flexible tube 3309, and an innerpuller 3305, is loaded onto the inversion support catheter 3307, andpartially deployed out of the intermediate catheter (sheath 3313). Thesub-assembly, which may be referred to as an inverting flexible tubesub-assembly is removable from the inversion support catheter, and maybe removed from the inversion support catheter out of the intermediatecatheter after removing all or part of a clot; the intermediate catheter(sheath) may then be left in place while the intermediate catheter andinverting flexible tube sub-assembly may be removed from the vesselproximally. Once withdrawn, the sub-assembly may be removed from theinversion support catheter and a new sub-assembly may be loaded onto theinversion support catheter and inserted back through the intermediatecatheter to remove additional clot material. This is illustrated inFIGS. 33A-33E.

In FIG. 33A, the apparatus is shown partially deployed, with theinversion support catheter 3307 extending out of the sheath 3313, andthe flexible tube 3309 connected at one end to a split cuff 3311 and atthe other end to a puller (e.g., puller assembly, including a pullerwire 3305 and a puller catheter segment 3306). The cuff may be slid overthe inversion support catheter distally as the puller is drawnproximally (e.g., by pulling on the puller end 3356). Pulling the pullerproximally causes the flexible tube to roll and invert over the distalend of the inversion support catheter. In FIG. 33A, a guidewire 3341 maybe used, and passes through the catheter segment 3306 of the puller. Asdescribed in greater detail above, this may draw a clot into theinversion support catheter. Once the cuff reaches the distal end of theinversion support catheter, as shown in FIG. 33B, the cuff may splitapparat and roll and invert 3372 over the distal end of the inversionsupport catheter as well, into the inversion support catheter. As shownin FIG. 33C, the entire sub-assembly (e.g., the puller, flexible tube3309 and split cuff 3311 may then be housed within the inversion supportcatheter 3307, and withdrawn proximally out of the sheath 3313. Forexample, the proximal end of the inversion support catheter may includea handle or grip 3361, allowing it to be advanced and/or withdrawn fromoutside of the patient. The entire sub-assembly and/or inversion supportcatheter may be removed proximally out of the patient.

Once removed, the inverting flexible tube sub-assembly may then beremoved, along with captured clot, from the inversion support catheter,and either a new inversion support-catheter pre-loaded with an invertingflexible tube sub-assembly may then be inserted into the sheath and backinto the vessel to capture any additional clot material, or the sameinversion support catheter may be re-loaded with a new invertingflexible tube sub-assembly, as shown in FIG. 33D and alternativevariation in FIG. 33E.

In FIG. 33D, a new inverting flexible tube sub-assembly 3360, includingthe puller (puller assembly including pull wire 3305 and pull catheter3306), flexible tube 3309 and cuff 3311, is loaded 3374 into the distalend of the inversion support catheter 3307. The variation shown in FIG.33E is similar to that shown in FIG. 33D, but the cuff 3311′ isun-inverted, and therefore loads on the outer surface of the inversionsupport catheter. As the loaded inversion support catheter is drivenback through the sheath, the flexible tube 3309 and cuff may be drivenproximally, so that it prepared to be withdrawn proximally by the pullerto capture clot by the time it reaches the distal end region of thesheath.

In any of these variations, a guidewire may be use to insert and guideinsertion of the inverting flexible tube sub-assembly and/or inversionsupport catheter to the clot material.

The steps of capturing clot, withdrawing the sub-assembly proximally andreloading anew sub-assembly, as illustrated in FIGS. 33A-33E, may berepeated as necessary to remove more clot material.

Alternatively, as mentioned above, any of the apparatuses describedherein may be configured to reusing inverting flexible tube sub-assemblyand other portions of the apparatus. For example, the apparatus may bedeployed to a clot, and used to remove at least a portion of the clot,and the clot, captured by the flexible tube, may be withdrawn out of thevessel, and ejected from the flexible tube, and the flexible tube (e.g.,the inverting flexible tube sub-assembly including the flexible tube)reloaded, reinserted and used to remove additional clot. An example ofthis is illustrated in FIGS. 34A-34C.

In FIG. 34A, a portion of clot 3490 has been captured by an apparatus.The apparatus may include an inversion support catheter 3407, a puller3405, a flexible tube 3409 and a cuff 3411. In this example, the pullerincludes a proximal handle region 3465 and the inversion supportcatheter includes a proximal handle region 3467. The apparatus has beenwithdrawn from out of the patient after grabbing the clot material inFIG. 34A. The clot material may then be ejected from the apparatus, asshown in FIG. 34B. In this example, the clot material is ejected bypulling the cuff proximally 3472 and/or by pushing the puller distally3474. In some variations, the clot may be ejected by both pushing thepuller distally and by pulling the cuff proximally. For example, in somevariations it may be beneficial to use an ejection apparatus 3522, asshown schematically in FIG. 35, to coordinate the relative motion of thepuller 3505 (or puller assembly) and the inversion support catheter3507, while drawing the cuff 3511 proximally. The ejection apparatus3522 couples to both the puller proximal handle 3565 and the inversionsupport catheter proximal handle 3567 and moves the two handles 3565 and3567 closer to each other 3572, as shown by the arrows. Force may alsobe provided (manually or automatically) to move the cuff 3511 proximallyto eject the clot material 3590 from the flexible tube 3509. Forexample, the ejection apparatus may be a mechanical apparatus includingone or more springs (e.g., extension springs) to assist in ejecting theclot material.

Once the clot is ejected, as shown in FIG. 34C, the apparatus isprepared for re-insertion, and may be inserted back into the patient(e.g., through an intermediate catheter with or without a guidewire) toremove additional clot material. An additional cover or sheath may beused to re-introduce the apparatus through the intermediate catheter.

When a feature or element is herein referred to as being “on” anotherfeature or element, it can be directly on the other feature or elementor intervening features and/or elements may also be present. Incontrast, when a feature or element is referred to as being “directlyon” another feature or element, there are no intervening features orelements present. It will also be understood that, when a feature orelement is referred to as being “connected”, “attached” or “coupled” toanother feature or element, it can be directly connected, attached orcoupled to the other feature or element or intervening features orelements may be present. In contrast, when a feature or element isreferred to as being “directly connected”, “directly attached” or“directly coupled” to another feature or element, there are nointervening features or elements present. Although described or shownwith respect to one embodiment, the features and elements so describedor shown can apply to other embodiments. It will also be appreciated bythose of skill in the art that references to a structure or feature thatis disposed “adjacent” another feature may have portions that overlap orunderlie the adjacent feature.

Terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention.For example, as used herein, the singular forms “a”, “an” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise. It will be further understood that the terms“comprises” and/or “comprising,” when used in this specification,specify the presence of stated features, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, steps, operations, elements, components, and/orgroups thereof. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items and may beabbreviated as “/”.

Spatially relative terms, such as “under”, “below”, “lower”, “over”,“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if a device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of over and under. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly”, “downwardly”, “vertical”, “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

Although the terms “first” and “second” may be used herein to describevarious features/elements (including steps), these features/elementsshould not be limited by these terms, unless the context indicatesotherwise. These terms may be used to distinguish one feature/elementfrom another feature/element. Thus, a first feature/element discussedbelow could be termed a second feature/element, and similarly, a secondfeature/element discussed below could be termed a first feature/elementwithout departing from the teachings of the present invention.

Throughout this specification and the claims which follow, unless thecontext requires otherwise, the word “comprise”, and variations such as“comprises” and “comprising” means various components can be co-jointlyemployed in the methods and articles (e.g., compositions and apparatusesincluding device and methods). For example, the term “comprising” willbe understood to imply the inclusion of any stated elements or steps butnot the exclusion of any other elements or steps.

In general, any of the apparatuses and methods described herein shouldbe understood to be inclusive, but all or a sub-set of the componentsand/or steps may alternatively be exclusive, and may be expressed as“consisting of” or alternatively “consisting essentially of” the variouscomponents, steps, sub-components or sub-steps.

As used herein in the specification and claims, including as used in theexamples and unless otherwise expressly specified, all numbers may beread as if prefaced by the word “about” or “approximately,” even if theterm does not expressly appear. The phrase “about” or “approximately”may be used when describing magnitude and/or position to indicate thatthe value and/or position described is within a reasonable expectedrange of values and/or positions. For example, a numeric value may havea value that is +/−0.1% of the stated value (or range of values), +/−1%of the stated value (or range of values), +/−2% of the stated value (orrange of values), +/−5% of the stated value (or range of values), +/−10%of the stated value (or range of values), etc. Any numerical valuesgiven herein should also be understood to include about or approximatelythat value, unless the context indicates otherwise. For example, if thevalue “10” is disclosed, then “about 10” is also disclosed. Anynumerical range recited herein is intended to include all sub-rangessubsumed therein. It is also understood that when a value is disclosedthat “less than or equal to” the value, “greater than or equal to thevalue” and possible ranges between values are also disclosed, asappropriately understood by the skilled artisan. For example, if thevalue “X” is disclosed the “less than or equal to X” as well as “greaterthan or equal to X” (e.g., where X is a numerical value) is alsodisclosed. It is also understood that the throughout the application,data is provided in a number of different formats, and that this data,represents endpoints and starting points, and ranges for any combinationof the data points. For example, if a particular data point “10” and aparticular data point “15” are disclosed, it is understood that greaterthan, greater than or equal to, less than, less than or equal to, andequal to 10 and 15 are considered disclosed as well as between 10 and15. It is also understood that each unit between two particular unitsare also disclosed. For example, if 10 and 15 are disclosed, then 11,12, 13, and 14 are also disclosed.

Although various illustrative embodiments are described above, any of anumber of changes may be made to various embodiments without departingfrom the scope of the invention as described by the claims. For example,the order in which various described method steps are performed mayoften be changed in alternative embodiments, and in other alternativeembodiments one or more method steps may be skipped altogether. Optionalfeatures of various device and system embodiments may be included insome embodiments and not in others. Therefore, the foregoing descriptionis provided primarily for exemplary purposes and should not beinterpreted to limit the scope of the invention as it is set forth inthe claims.

The examples and illustrations included herein show, by way ofillustration and not of limitation, specific embodiments in which thesubject matter may be practiced. As mentioned, other embodiments may beutilized and derived there from, such that structural and logicalsubstitutions and changes may be made without departing from the scopeof this disclosure. Such embodiments of the inventive subject matter maybe referred to herein individually or collectively by the term“invention” merely for convenience and without intending to voluntarilylimit the scope of this application to any single invention or inventiveconcept, if more than one is, in fact, disclosed. Thus, althoughspecific embodiments have been illustrated and described herein, anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations or variations of various embodiments.Combinations of the above embodiments, and other embodiments notspecifically described herein, will be apparent to those of skill in theart upon reviewing the above description.

What is claimed is:
 1. A method of removing a clot from a vessel, themethod comprising: advancing an inverting tube apparatus through avessel until a distal end of the inverting tube apparatus is proximateto a clot, wherein the inverting tube apparatus comprises anintermediate catheter, an inversion support catheter within a lumen ofthe intermediate catheter, a puller within a lumen of the inversionsupport catheter, and a flexible tube having a first end coupled at adistal end region of the puller and a second end that is free to moveover an outer surface of the inversion support catheter, wherein theflexible tube extends proximally between the intermediate catheter andthe inversion support catheter; pulling the puller proximally to rollthe flexible tube over a distal end of the inversion support catheter sothat the flexible tube inverts over a distal end of the inversionsupport catheter, captures the clot, and pulls the clot proximally intothe inversion support catheter, wherein the second end reaches thedistal end of the inversion support catheter while a portion of the clotextends distally from the inversion support catheter; and withdrawing,after the second end reaches the distal end of the inversion supportcatheter, the inversion support catheter and puller with the clotattached proximally into the intermediate catheter until the entire clotis within the intermediate catheter.
 2. The method of claim 1, furthercomprising applying suction through the inverting tube apparatus whenwithdrawing the inversion support catheter and puller with the clotattached proximally into the intermediate catheter.
 3. The method ofclaim 1, wherein the second end of the flexible tube comprises a cuffthat is less flexible that a region of the flexible tube adjacent to thecuff.
 4. The method of claim 1, wherein the second end of the flexibletube comprises a cuff having longitudinal slits along its length.
 5. Themethod of claim 3, wherein the cuff comprises a polymeric material. 6.The method of claim 3, further comprising limiting the puller to stopthe puller from moving proximally when or before the cuff reaches thedistal end of the inversion support catheter.
 7. The method of claim 3,further comprising moving the intermediate catheter distally past thecuff to invert the cuff over the distal end of the inversion supportcatheter.
 8. A method of removing a clot from a vessel, the methodcomprising: advancing an inverting tube apparatus through a vessel untila distal end of the inverting tube apparatus is proximate to a clot,wherein the inverting tube apparatus comprises an intermediate catheter,an inversion support catheter within a lumen of the intermediatecatheter, a puller within a lumen of the inversion support catheter, anda flexible tube having a first end coupled at a distal end region of thepuller and a second end comprising a cuff that is less flexible that aregion of the flexible tube adjacent to the cuff, wherein the flexibletube extends proximally between the intermediate catheter and theinversion support catheter; pulling the puller proximally to roll theflexible tube over a distal end of the inversion support catheter sothat the flexible tube inverts over a distal end of the inversionsupport catheter, captures the clot, and pulls the clot proximally intothe inversion support catheter; stopping pulling the puller from movingproximally when or before the cuff reaches the distal end of theinversion support catheter; moving the intermediate catheter distallypast the cuff to invert the cuff over the distal end of the inversionsupport catheter; and withdrawing the inversion support catheter andpuller with the clot attached proximally into the intermediate catheter.9. The method of claim 8, wherein the cuff comprises one or more slitsalong its length extending in a proximal-to-distal direction.
 10. Themethod of claim 8, wherein the cuff comprises a polymeric material. 11.A method of removing a clot from a vessel having an inner diameter (ID),the method comprising: advancing an inverting tube apparatus through thevessel until a distal end of the inverting tube apparatus is proximateto a clot, wherein the inverting tube apparatus comprises anintermediate catheter, an inversion support catheter within a lumen ofthe intermediate catheter, a puller within a lumen of the supportcatheter, and a knitted tube having a first end coupled at a distal endregion of the puller and a second end, wherein the knitted tube extendsbetween the intermediate catheter and the inversion support catheter;further wherein the knitted tube comprises a filament knitted to form aplurality of interlocking loop stitches, wherein each loop stitch has astitch length that is between the difference of 25% of the ID and onehalf the outer diameter (OD) of the inversion support catheter and 65%of the ID and one half of the OD of the inversion support catheter;pulling the puller proximally to roll the knitted tube over the distalend of the inversion support catheter so that the knitted tube invertsover a distal end of the inversion support catheter driving the loopstitches outward, captures the clot, and pulls the clot proximally intothe inversion support catheter.
 12. The method of claim 11, wherein theknitted tube extends over the inversion support catheter with an innerdiameter that is within 20% of the OD the inversion support catheter.13. The method of claim 11, wherein the second end of the knitted tubecomprises a cuff that is less flexible that a region of the knitted tubeadjacent to the cuff.
 14. The method of claim 11, wherein each loopstitch has a stitch length that is between the difference of 30% of theID and one half the OD of the inversion support catheter and 60% of theID and one half of the OD of the inversion support catheter.
 15. Themethod of claim 11, wherein each loop stitch has a stitch length that isbetween the difference of 35% of the ID and one half the OD of theinversion support catheter and 50% of the ID and one half of the OD ofthe inversion support catheter.
 16. The method of claim 11, wherein eachloop stitch has a stitch length that is between the difference of 40% ofthe ID and one half the OD of the inversion support catheter and 45% ofthe ID and one half of the OD of the inversion support catheter.
 17. Themethod of claim 11, wherein each loop stitch has a stitch length that isbetween the difference of 25% of the ID and one half the OD of theinversion support catheter and 45% of the ID and one half of the OD ofthe inversion support catheter.